ID NRAM_I00A0 Reviewed; 469 AA. AC Q8QPK2; DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 08-NOV-2023, entry version 97. 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/Duck/Hong Kong/2986.1/2000 H5N1 genotype C). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=176674; 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=11878904; DOI=10.1006/viro.2001.1207; RA Guan Y., Peiris M., Kong K.F., Dyrting K.C., Ellis T.M., Sit T., RA Zhang L.J., Shortridge K.F.; RT "H5N1 influenza viruses isolated from geese in Southeastern China: evidence RT for genetic reassortment and interspecies transmission to ducks."; RL Virology 292:16-23(2002). 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 --------------------------------------------------------------------------- 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; AY059490; AAL31396.1; -; Genomic_RNA. DR SMR; Q8QPK2; -. DR CAZy; GH34; Glycoside Hydrolase Family 34. DR GlyCosmos; Q8QPK2; 8 sites, No reported glycans. DR Proteomes; UP000008285; 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 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..469 FT /note="Neuraminidase" FT /id="PRO_0000310929" 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..469 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..90 FT /note="Hypervariable stalk region" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 91..469 FT /note="Head of neuraminidase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 151 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 402 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 118 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 152 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 277..278 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 293 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 294 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 298 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 324 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 368 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 58 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 63 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 68 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 88 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 146 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 235 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 386 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 92..417 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 124..129 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 184..231 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 233..238 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 279..292 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 281..290 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 318..335 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 421..446 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" SQ SEQUENCE 469 AA; 51366 MW; DF455ADB29FF49B6 CRC64; MNPNQKIITI GSICMVIGIV SLMLQIGNII SIWVSHSIQT GNQHQAEPCN QSIITYENNT WVNQTYVNIS NTNFLTEKAV ASVTLAGNSS LCPISGWAVY SKDNGIRIGS KGDVFVIREP FISCSHLECR TFFLTQGALL NDKHSNGTVK DRSPYRTLMS CPVGEAPSPY NSRFESVAWS ASACHDGTSW LTIGISGPDN GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT VMTDGPSNGQ ASYKIFKIEK GKVVKSVELN APNYHYEECS CYPDAGEITC VCRDNWHGSN RPWVSFNQNL EYQIGYICSG VFGDNPRPND GTGSCGPVSP NGAYGIKGFS FKYGNGVWIG RTKSTNSRSG FEMIWDPNGW TGTDSNFSVK QDIVAITDWS GYSGSFVQHP ELTGLDCIRP CFWVELIRGR PKESTIWTSG SSISFCGVNS DTVGWSWPDG AELPFTIDK //