ID A0A291IDB7_9INFA Unreviewed; 459 AA. AC A0A291IDB7; DT 20-DEC-2017, integrated into UniProtKB/TrEMBL. DT 20-DEC-2017, sequence version 1. DT 03-AUG-2022, entry version 22. DE RecName: Full=Neuraminidase {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; DE EC=3.2.1.18 {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; GN Name=NA {ECO:0000256|HAMAP-Rule:MF_04071, GN ECO:0000256|RuleBase:RU361252, ECO:0000313|EMBL:ATG88194.1}; OS Influenza A virus (A/poultry/China/XY01.6/2016(H5N6)). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=2042253 {ECO:0000313|EMBL:ATG88194.1}; RN [1] {ECO:0000313|EMBL:ATG88194.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/poultry/China/XY01.6/2016 {ECO:0000313|EMBL:ATG88194.1}; RA Zhao Z.; RT "Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicity RT Pathogenicities and Transmissibilities in Mammals."; RL Sci. Rep. 0:0-0(2017). 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 moities 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:0000256|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:0000256|HAMAP- CC Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000256|ARBA:ARBA00001913, CC ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; 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:0000256|HAMAP-Rule:MF_04071}. CC -!- SUBUNIT: Homotetramer. {ECO:0000256|ARBA:ARBA00011881, CC ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004606}; Single- CC pass type II membrane protein {ECO:0000256|ARBA:ARBA00004606}. Virion CC membrane {ECO:0000256|HAMAP-Rule:MF_04071}. Host apical cell membrane CC {ECO:0000256|HAMAP-Rule:MF_04071}; Single-pass type II membrane protein CC {ECO:0000256|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:0000256|HAMAP- CC Rule:MF_04071}. CC -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis. CC Possess 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:0000256|HAMAP-Rule:MF_04071}. CC -!- PTM: N-glycosylated. {ECO:0000256|HAMAP-Rule:MF_04071, CC ECO:0000256|RuleBase:RU361252}. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family. CC {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|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; MG029173; ATG88194.1; -; Viral_cRNA. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of 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:UniProtKB-UniRule. DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule. 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; SSF50939; 1. PE 3: Inferred from homology; KW Calcium {ECO:0000256|ARBA:ARBA00022837, ECO:0000256|HAMAP-Rule:MF_04071}; KW Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04071}; KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180, ECO:0000256|HAMAP- KW Rule:MF_04071}; KW Glycosidase {ECO:0000256|ARBA:ARBA00023295, ECO:0000256|HAMAP- KW Rule:MF_04071}; KW Host cell membrane {ECO:0000256|ARBA:ARBA00022511, ECO:0000256|HAMAP- KW Rule:MF_04071}; KW Host membrane {ECO:0000256|ARBA:ARBA00022870, ECO:0000256|HAMAP- KW Rule:MF_04071}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_04071}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|HAMAP-Rule:MF_04071}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP- KW Rule:MF_04071}; KW Signal-anchor {ECO:0000256|ARBA:ARBA00022968, ECO:0000256|HAMAP- KW Rule:MF_04071}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|HAMAP- KW Rule:MF_04071}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, ECO:0000256|HAMAP- KW Rule:MF_04071}; KW Virion {ECO:0000256|ARBA:ARBA00022844, ECO:0000256|HAMAP-Rule:MF_04071}. FT TRANSMEM 7..31 FT /note="Helical" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT REGION 11..33 FT /note="Involved in apical transport and lipid raft FT association" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT REGION 80..459 FT /note="Head of neuraminidase" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT REGION 266..267 FT /note="Substrate binding" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT ACT_SITE 140 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT ACT_SITE 395 FT /note="Nucleophile" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 107 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 141 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 282 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 283 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 287 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 314 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 361 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 113..118 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 173..220 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 222..227 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 268..281 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 270..279 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" SQ SEQUENCE 459 AA; 50744 MW; A942739EE62FE77D CRC64; MNPNQKITCI SATGVTLSVV SLLIGITNLG LNIGLHYKVS DSTTMNIPNM NETNPTTTNI TNIVMNKNEE RTFLKLTKPL CEVNSWHILS KDNAIRIGED AHILVTREPY LSCDPQGCRM FALSQGTTLR GQHANGTIHD RSPFRALISW EMGQAPSPYN TRAECIGWSS TSCHDGISRM SICISGPNNN ASAVVWYRGR PVTEIPSWAG NILRTQESEC VCHKGICPVV MTDGPANSKA ATKIIYFKEG KIQKTEELQG NAQHIEECSC YGAARMIKCV CRDNWKGANR PIITIDPEMM THTSKYLCSK ILTDTSRPND PTNGNCDAPI TGGSPDPGVK GFAFLDGENS WLGRTISKDS RSGYEMLKVP NAEIDTQSGP ISYQLIVNNQ NWSGYSGAFI DYWANKECFN PCFYVELIRG RPKESGVLWT SNSMVALCGS RERLGSWSWH DGAEIIYFK //