ID B1A803_9INFA Unreviewed; 468 AA. AC B1A803; DT 08-APR-2008, integrated into UniProtKB/TrEMBL. DT 08-APR-2008, sequence version 1. DT 02-JUN-2021, entry version 72. 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:ACA04654.1}; OS Influenza A virus (A/duck/Eastern China/488/2003(H10N3)). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=503313 {ECO:0000313|EMBL:ACA04654.1}; RN [1] {ECO:0000313|EMBL:ACA04654.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/duck/Eastern China/488/2003 {ECO:0000313|EMBL:ACA04654.1}; RA Qiu B.-F., Liu W.-J., Peng D.-X., Hu S.-L., Tang Y.-H., Liu X.-F.; RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:ACA04654.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/duck/Eastern China/488/2003 {ECO:0000313|EMBL:ACA04654.1}; RX PubMed=18984006; DOI=10.1016/j.jviromet.2008.10.001; RA Qiu B.F., Liu W.J., Peng D.X., Hu S.L., Tang Y.H., Liu X.F.; RT "A reverse transcription-PCR for subtyping of the neuraminidase of avian RT influenza viruses."; RL J. Virol. Methods 155:193-198(2009). CC -!- FUNCTION: Catalyzes the removal of terminal sialic acid residues from CC viral and cellular glycoconjugates. {ECO:0000256|RuleBase:RU361252}. 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, CC ECO:0000256|RuleBase:RU361252}. Host apical cell membrane CC {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; CC Single-pass type II membrane protein {ECO:0000256|HAMAP-Rule:MF_04071, CC ECO:0000256|RuleBase:RU361252}. Note=Preferentially accumulates at the CC apical plasma membrane in infected polarized epithelial cells, which is CC the virus assembly site. Uses lipid rafts for cell surface transport CC and apical sorting. In the virion, forms a mushroom-shaped spike on the CC surface of the membrane. {ECO:0000256|HAMAP-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; EU429712; ACA04654.1; -; mRNA. DR CAZy; GH34; Glycoside Hydrolase Family 34. 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 2: Evidence at transcript level; 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 90..468 FT /note="Head of neuraminidase" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT REGION 277..278 FT /note="Substrate binding" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT ACT_SITE 150 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT ACT_SITE 404 FT /note="Nucleophile" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT METAL 293 FT /note="Calcium; via carbonyl oxygen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT METAL 297 FT /note="Calcium; via carbonyl oxygen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT METAL 323 FT /note="Calcium" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 117 FT /note="Substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 151 FT /note="Substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 292 FT /note="Substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 369 FT /note="Substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 123..128 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 183..230 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 232..237 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" SQ SEQUENCE 468 AA; 51631 MW; DA1216C047E89C94 CRC64; MNPNQKITTI GVVSTTLSTI ALLIGIGNLI FNTVIHEKIG DHQTVVYPTI TAPVVPNCSD TIITYNNTVV NNITTIITKA ETHFKSSLPL CPFRGFFPFH KDNAIRLGEN KNVIATREPY VSCDNDDCWS FALAQGALLG TKHSNGTIKD RTPYRSLIRF PIGTAPVLGN YKEICVAWSS SSCFDGKEWM HVCMTGNDND ASGQIMYAGK MTDSIKSWRK DILRTQESEC QCIDGTCVVA VTDGPAASSA DHRIYWIREG KVLKYENIPK TKIQHLEECS CYVDIDVYCI CRDNWKGSNR PWMRINNETI LETGYVCSKF HSDTPRPADP STVSCDSPSN VNGGPGVKGF GFKTGNDVWL GRTVSTSGRS GFEIIKVTEG WINSPNHAKS VTQTLVSNND WSGYSGSFIV ENNGCFQPCF YIELIRGRPN KNDDVSWTSN SIVTFCGLDN EPGSGNWPDG SNIGFMPK //