ID F2NZA9_9INFA Unreviewed; 470 AA. AC F2NZA9; DT 31-MAY-2011, integrated into UniProtKB/TrEMBL. DT 31-MAY-2011, sequence version 1. DT 28-JUN-2023, entry version 61. 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:ADZ53101.1}; OS Influenza A virus (A/Hong Kong/62768/2008(H1N1)). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=997478 {ECO:0000313|EMBL:ADZ53101.1}; RN [1] {ECO:0000313|EMBL:ADZ53101.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/Hong Kong/62768/2008 {ECO:0000313|EMBL:ADZ53101.1}; RA Wu W.L., Lau S.Y., Wang G., Chen Y., Song W., Wang P., Mok B.W.Y., Tai H., RA Wen X., Guan Y., Lin T., Yuen K.Y., Chen H.; RT "Mechanism for the emergence and prevalence of H1N1 influenza virus RT carrying H275Y oseltamivir resistance mutation."; RL Submitted (MAR-2011) to the EMBL/GenBank/DDBJ databases. 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; CY087279; ADZ53101.1; -; Viral_cRNA. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. 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 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 {ECO:0000256|ARBA:ARBA00022837, ECO:0000256|HAMAP-Rule:MF_04071}; KW Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04071}; KW Glycoprotein {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252}; 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|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_04071}; KW Membrane {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|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}. FT TRANSMEM 7..34 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 91..470 FT /note="Head of neuraminidase" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT ACT_SITE 151 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT ACT_SITE 402 FT /note="Nucleophile" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 118 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 152 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 277..278 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 293 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 294 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 298 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 324 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 344 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 368 FT /ligand="substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 92..417 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 124..129 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 184..231 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 233..238 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 279..292 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 281..290 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 318..335 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" SQ SEQUENCE 470 AA; 51623 MW; 56C4E20257DEA044 CRC64; MNPNQKIITI GSISIAIGII SLMLQIGNII SIWASHSIQT GSQNNTGICN QRIITYENST WVNHTYVNIN NTKVVAGEDK TSVTLAGNSS LCSISGWAIN TKDNSIRIGS KGDVFVIREP FISCSHLECR TFFLTQGALL NDKHSNGTVK DRSPYRALMS CPLGEAPSPY NSKFESVAWS ASACHDGMGW LTIGISGPDN GAVAVLKYNG IITGTIKSWK KQILRTQESE CVCMNGSCFT IMTDGPSNKA ASYKIFKIEK GKVTKSIELN APNFYYEECS CYPDTGIVMC VCRDNWHGSN RPWVSFNQNL DYQIGYICSG VFGDNPRPED GEGSCNPVTV DGANGVKGFS YKYGNGVWIG RTKSNRLRKG FEMIWDPNGW TNTDSDFSVK QDVVAITDWS GYSGSFVQHP ELTGLDCIRP CFWVELVRGL PRENTTIWTS GSSISFCGVN SDTANWSWPD GAELPFTIDK //