ID NRAM_I83A6 Reviewed; 449 AA. AC P09573; Q0A2D4; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 06-MAR-2007, sequence version 2. DT 10-JUN-2026, entry version 138. 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/Chicken/Pennsylvania/1370/1983 H5N2). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=385617; OH NCBI_TaxID=8782; Aves. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=2414922; DOI=10.1016/0042-6822(85)90226-0; RA Deshpande K.L., Naeve C.W., Webster R.G.; RT "The neuraminidases of the virulent and avirulent A/Chicken/Pennsylvania/83 RT (H5N2) influenza A viruses: sequence and antigenic analyses."; RL Virology 147:49-60(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=16439620; DOI=10.1126/science.1121586; RA Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., Finkelstein D.B., RA Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., Webster R.G., Hoffmann E., RA Krauss S., Zheng J., Zhang Z., Naeve C.W.; RT "Large-scale sequence analysis of avian influenza isolates."; RL Science 311:1576-1580(2006). RN [3] 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 [4] 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 [5] 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 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; M12051; AAA43424.1; -; Genomic_RNA. DR EMBL; CY015110; ABI85148.1; -; Genomic_RNA. DR SMR; P09573; -. DR GlyCosmos; P09573; 8 sites, No reported glycans. 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:0004308; F:exo-alpha-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..449 FT /note="Neuraminidase" FT /id="PRO_0000078680" FT TOPO_DOM 1..6 FT /note="Intravirion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT TRANSMEM 7..29 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT TOPO_DOM 30..449 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..68 FT /note="Hypervariable stalk region" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 71..449 FT /note="Head of neuraminidase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 305..330 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 131 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 386 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 98 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 132 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 256..257 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 272 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 273 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 277 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 304 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 351 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 32 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 66 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 126 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 180 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 214 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 382 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 72..397 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 104..109 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 163..210 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 212..217 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 258..271 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 260..269 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 298..317 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 401..427 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CONFLICT 42 FT /note="R -> G (in Ref. 1; AAA43424)" FT CONFLICT 122 FT /note="N -> H (in Ref. 1; AAA43424)" FT CONFLICT 160 FT /note="S -> R (in Ref. 1; AAA43424)" FT CONFLICT 232 FT /note="I -> T (in Ref. 1; AAA43424)" FT CONFLICT 263..265 FT /note="RYP -> KSYL (in Ref. 1; AAA43424)" FT CONFLICT 283 FT /note="I -> KL (in Ref. 1; AAA43424)" FT CONFLICT 361 FT /note="G -> S (in Ref. 1; AAA43424)" FT CONFLICT 420 FT /note="S -> T (in Ref. 1; AAA43424)" SQ SEQUENCE 449 AA; 49693 MW; DC716FBFB147ADA1 CRC64; MNPNQKIITI GSVSLTIATV CFLMQIAILA TNVTLHFRQN ERSIPAYNQT TPCKPIIIER NIKYRNWSKP QCQITGFAPF SKDNSIRLSA GGGIWVTREP YVSCDPSKCY QFALGQGTTL DNNHSNGTIH DRTPHRTLLM NELGVPFHLG TRQVCIAWSS SSCHDGKAWL HVCVTGDDRN ATASFIYNGM LVDSIGSWSQ NILRTQESEC VCINGTCTVV MTDGSASGKA DIRILFIREG KIVHISPLSG SAQHIEECSC YPRYPNVRCV CRDNWKGSNR PVIDINMADY SIDSSYVCSG LVGDTPRNDD SSSSSNCRDP NNERGNPGVK GWAFDIGDDV WMGRTISKDS RSGYETFRVI GGWATANSKS QTNRQVIVDN NNWSGYSGIF SVESKSCINR CFYVELIRGR PQETRVWWTS NSIVVFCGTS GTYGTGSWPD GANINFMPL //