ID NRAM_I79A7 Reviewed; 470 AA. AC Q6XV43; DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 08-NOV-2023, entry version 92. 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/Grey teal/Australia/2/1979 H4N4). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=402464; OH NCBI_TaxID=8782; Aves. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RA Webby R.J., Humberd J.L., Krauss S.L.; RT "Genetic analysis of multiple N3, N4, and N6 influenza A virus RT neuraminidase genes."; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. 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; AY207533; AAO62047.1; -; Genomic_DNA. DR SMR; Q6XV43; -. DR CAZy; GH34; Glycoside Hydrolase Family 34. DR GlyCosmos; Q6XV43; 7 sites, No reported glycans. DR PRO; PR:Q6XV43; -. DR Proteomes; UP000008575; 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 Gene3D; 2.120.10.10; -; 1. DR HAMAP; MF_04071; INFV_NRAM; 1. DR InterPro; IPR001860; Glyco_hydro_34. 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..470 FT /note="Neuraminidase" FT /id="PRO_0000280132" 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..470 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..88 FT /note="Hypervariable stalk region" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 90..470 FT /note="Head of neuraminidase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 150 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 403 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 117 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 151 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 276..277 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 292 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 293 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 297 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 323 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 369 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 57 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 62 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 145 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 399 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 417 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 91..418 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 123..128 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 183..230 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 232..237 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 278..291 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 280..289 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 317..334 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 422..447 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" SQ SEQUENCE 470 AA; 51713 MW; DEDE5BB5485BBA6A CRC64; MNPNQKIITI GSVSIVLTTV GLLLQITSLC SIWFSHYNQV TQTNGQPCSN DTINYYNETF VNVTNVQNNY TTITEPSIPQ AIHYSSGRDL CPVKGWAPLS KDNGIRIGSR GEVFVIREPF ISCSINECRT FFLTQGALLN DKHSNGTVKD RSPFRTLMSC PIGVAPSPSN SRFESVAWSA TACSDGPGWL TLGITGPDTT AVAVLKYNGV ITDTLKSWKG NIMRTQESEC VCQDEFCYTL VTDGPSDAQA FYKILKIKKG KIVGAKDVDA TGFHFEECSC YPSGENVECV CRDNWRGSNR PWIRFNSDLD YQIGYVCSGV FGDNPRPVDG TGSCNSPVNN GKGRYGVKGF SFRYGDGVWI GRTKSLESRS GFEMVWDANG WVSTDKDSNG VQDIIDNDNW SGYSGSFSIR GETTGRNCTV PCFWVEMIRG QPKEKTIWTS GSSIAFCGVN SDTTSWSWPD GALLPFDIDK //