ID NRAM_I97A1 Reviewed; 450 AA. AC Q9W7Y7; O89527; Q9WA99; DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 2. DT 08-NOV-2023, entry version 118. DE RecName: Full=Neuraminidase {ECO:0000255|HAMAP-Rule:MF_04071}; DE EC=3.2.1.18 {ECO:0000255|HAMAP-Rule:MF_04071}; GN Name=NA {ECO:0000255|HAMAP-Rule:MF_04071}; OS Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=130763; 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 [MRNA]. RX PubMed=9482438; DOI=10.1016/s0140-6736(97)11212-0; RA Claas E.C.J., Osterhaus A.D., van Beek R., De Jong J.C., Rimmelzwaan G.F., RA Senne D.A., Krauss S., Shortridge K.F., Webster R.G.; RT "Human influenza A H5N1 virus related to a highly pathogenic avian RT influenza virus."; RL Lancet 351:472-477(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=9430591; DOI=10.1126/science.279.5349.393; RA Subbarao K., Klimov A., Katz J., Regnery H., Lim W., Hall H., Perdue M., RA Swayne D., Bender C., Huang J., Hemphill M., Rowe T., Shaw M., Xu X., RA Fukuda K., Cox N.; RT "Characterization of an avian influenza A (H5N1) virus isolated from a RT child with a fatal respiratory illness."; RL Science 279:393-396(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=9658115; DOI=10.1128/jvi.72.8.6678-6688.1998; RA Suarez D.L., Perdue M.L., Cox N., Rowe T., Bender C., Huang J., RA Swayne D.E.; RT "Comparisons of highly virulent H5N1 influenza A viruses isolated from RT humans and chickens from Hong Kong."; RL J. Virol. 72:6678-6688(1998). RN [4] RP REVIEW. RX PubMed=15567494; DOI=10.1016/j.virusres.2004.08.012; RA Nayak D.P., Hui E.K., Barman S.; RT "Assembly and budding of influenza virus."; RL Virus Res. 106:147-165(2004). RN [5] RP REVIEW. RX PubMed=16192481; DOI=10.1056/nejmra050740; RA Moscona A.; RT "Neuraminidase inhibitors for influenza."; RL N. Engl. J. Med. 353:1363-1373(2005). RN [6] RP REVIEW. RX PubMed=15744059; DOI=10.1248/bpb.28.399; RA Suzuki Y.; RT "Sialobiology of influenza: molecular mechanism of host range variation of RT influenza viruses."; RL Biol. Pharm. Bull. 28:399-408(2005). 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 consist 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 -!- SEQUENCE CAUTION: CC Sequence=AAC34264.1; Type=Erroneous initiation; 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; AF028708; AAC40507.1; -; mRNA. DR EMBL; AF036357; AAC34264.1; ALT_INIT; Genomic_RNA. DR EMBL; AF046089; AAC32089.1; -; Genomic_RNA. DR SMR; Q9W7Y7; -. DR CAZy; GH34; Glycoside Hydrolase Family 34. DR GlyCosmos; Q9W7Y7; 4 sites, No reported glycans. DR Proteomes; UP000008587; Genome. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0052795; F:exo-alpha-(2->6)-sialidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0052796; F:exo-alpha-(2->8)-sialidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule. DR CDD; cd15483; Influenza_NA; 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 2: Evidence at transcript level; 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..450 FT /note="Neuraminidase" FT /id="PRO_0000078700" FT TOPO_DOM 1..6 FT /note="Intravirion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT TRANSMEM 7..27 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT TOPO_DOM 28..450 FT /note="Virion surface" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 11..33 FT /note="Involved in apical transport and lipid raft FT association" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 36..71 FT /note="Hypervariable stalk region" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 72..450 FT /note="Head of neuraminidase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 132 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 383 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 99 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 133 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 258..259 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 274 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 275 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" 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 305 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 349 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 50 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 69 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 127 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 216 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 73..398 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 105..110 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 165..212 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 214..219 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 260..273 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 262..271 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 299..316 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 402..427 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CONFLICT 441..443 FT /note="GAD -> DAE (in Ref. 2; AAC34264)" FT CONFLICT 443 FT /note="D -> E (in Ref. 3; AAC32089)" SQ SEQUENCE 450 AA; 49503 MW; 0DCB54FCB6E7C8F2 CRC64; MNPNQKIITI GSICMVVGII SLMLQIGNII SVWVSHIIQT WHPNQPEPCN QSINFYTEQA AASVTLAGNS SLCPISGWAI YSKDNSIRIG SKGDVFVIRE PFISCSHLEC RTFFLTQGAL LNDKHSNGTV KDRSPYRTLM SCPVGEAPSP YNSRFESVAW SASACHDGIS WLTIGISGPD NGAVAVLKYN GIITDTIKSW RNNILRTQES ECACVNGSCF TVMTDGPSNE QASYKIFKIE KGRVVKSVEL NAPNYHYEEC SCYPDAGEIT CVCRDNWHGS NRPWVSFNQN LEYQIGYICS GVFGDSPRPN DGTGSCGPVS LNGAYGVKGF SFKYGNGVWI GRTKSTSSRS GFEMIWDPNG WTETDSSFSL KQDIIAITDW SGYSGSFIQH PELTGLNCMR PCFWVELIRG RPKEKTIWTS GSSISFCGVN SDTVGWSWPD GADLPFTIDK //