ID NRAM_I82A7 Reviewed; 446 AA. AC Q67344; DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 08-NOV-2023, entry version 108. 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/Swine/Hong Kong/127/1982 H3N2). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=384483; OH NCBI_TaxID=8782; Aves. OH NCBI_TaxID=9721; Cetacea (whales). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9709; Phocidae (true seals). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=7897351; DOI=10.1099/0022-1317-76-3-613; RA Nerome K., Kanegae Y., Shortridge K.F., Sugita S., Ishida M.; RT "Genetic analysis of porcine H3N2 viruses originating in Southern China."; RL J. Gen. Virol. 76:613-624(1995). RN [2] 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 [3] 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 [4] 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 --------------------------------------------------------------------------- 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; D21194; BAA04730.1; -; Genomic_RNA. DR SMR; Q67344; -. DR BindingDB; Q67344; -. DR CAZy; GH34; Glycoside Hydrolase Family 34. DR GlyCosmos; Q67344; 7 sites, No reported glycans. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IEA:UniProtKB-EC. DR GO; GO:0052795; F:exo-alpha-(2->6)-sialidase activity; IEA:UniProtKB-EC. DR GO; GO:0052796; F:exo-alpha-(2->8)-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 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..446 FT /note="Neuraminidase" FT /id="PRO_0000280158" FT REGION 13..65 FT /note="Hypervariable stalk region" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 68..446 FT /note="Head of neuraminidase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 304..327 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 304..319 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 128 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 95 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 129 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 253..254 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 269 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 270 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 274 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 301 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 348 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 47 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 123 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 177 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 211 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 379 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 69..394 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 101..106 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 160..207 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 209..214 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 255..268 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 257..266 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 295..314 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 398..424 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT NON_TER 1 SQ SEQUENCE 446 AA; 49915 MW; B3E31B09E6728A9D CRC64; MQIAILVTTV TLHFNQYECD SLADNQVMPC EPIIIERNIT EIIYLTNTTI EKEICPKLME YRNWSRPQCK ITGFAPFSKD NSIRLSAGGD IWVTREPYVS CDPGKCYQFA LGQGTTLDNK HSNDTIHDRI PHRTLLMNEL GVPFHLGTRQ VCIAWSSSSC HDGKAWLHVC VTGDDKNATA SFIYDGRLVD SMGSWSQNIL RTQESECVCI NGTCTVVMTD GSASGRADTR ILFIEEGKIV HISPLSGSAQ HVEECSCYPR YPSVRCICRD NWKGSNRPIV DINIKDYSID SRYVCSGLVG DTPRNNDRSS SSDCKNPNND KGNHGVKGWA FDDGNDVWMG RTISKDSRSG YETFKVIDGW STPNSKSQIN RQVIVDRDNR SGYSGIFSVE SKGCINRCFY VELIRGRKQE TRVWWTSSSI VVFCGTSGTY GKGSWPDGAN INFMPI //