ID I0AWZ8_9INFA Unreviewed; 466 AA. AC I0AWZ8; DT 13-JUN-2012, integrated into UniProtKB/TrEMBL. DT 13-JUN-2012, sequence version 1. DT 02-DEC-2020, entry version 51. 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:AFH53512.1}; OS Influenza A virus (A/chicken/Guangdong/LYH12/2011(H9N2)). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=1161301 {ECO:0000313|EMBL:AFH53512.1}; RN [1] {ECO:0000313|EMBL:AFH53512.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/chicken/Guangdong/LYH12/2011 {ECO:0000313|EMBL:AFH53512.1}; RX PubMed=24682938; DOI=10.1007/s11262-014-1060-1; RA Xue Y., Wang J.L., Yan Z.Q., Li G.W., Chen S.Y., Zhang X.B., Qin J.P., RA Li H.Y., Chang S., Chen F., Bee Y.Z., Xie Q.M.; RT "Sequence and phylogenetic analysis of surface protein genes of emerging RT H9N2 influenza viruses isolated from poultry in two geographical regions of RT China."; RL Virus Genes 48:479-485(2014). 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; JQ770145; AFH53512.1; -; 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 CDD; cd15483; Influenza_NA; 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; SSF50939; 1. PE 3: Inferred from homology; KW Calcium {ECO:0000256|ARBA:ARBA00022837, ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252}; KW Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04071}; KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180, ECO:0000256|HAMAP- KW Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; KW Glycosidase {ECO:0000256|ARBA:ARBA00023295, ECO:0000256|HAMAP- KW Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; KW Host cell membrane {ECO:0000256|ARBA:ARBA00022511, ECO:0000256|HAMAP- KW Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; KW Host membrane {ECO:0000256|ARBA:ARBA00022870, ECO:0000256|HAMAP- KW Rule:MF_04071, ECO:0000256|RuleBase:RU361252}; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252}; 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, ECO:0000256|RuleBase:RU361252}; 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, KW ECO:0000256|RuleBase:RU361252}. FT TRANSMEM 7..29 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 88..466 FT /note="Head of neuraminidase" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT REGION 273..274 FT /note="Substrate binding" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT REGION 323..347 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 323..338 FT /note="Polar" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 148 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT ACT_SITE 403 FT /note="Nucleophile" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT METAL 290 FT /note="Calcium; via carbonyl oxygen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT METAL 294 FT /note="Calcium; via carbonyl oxygen" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT METAL 321 FT /note="Calcium" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 115 FT /note="Substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 149 FT /note="Substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 289 FT /note="Substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT BINDING 368 FT /note="Substrate" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 89..414 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 121..126 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 180..227 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 229..234 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 275..288 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" FT DISULFID 277..286 FT /evidence="ECO:0000256|HAMAP-Rule:MF_04071" SQ SEQUENCE 466 AA; 51612 MW; 9CCCDBDD25864292 CRC64; MNPNQKIIAI GSVSLIIAII CLLMQIAILT TTMTLHFRQN ECSNPSNNQV MPCEPIIIER NTVHLNSTTI EREICPKVAE YKNWSKPQCQ ITGFAPFSKD NSIRLSAGGD IWVTREPYVS CSLDKCYHFA LGQGTTLKNK HSNGTTHDRT PHRTLLMNEL GVPFHLGTKQ VCIAWSSSSC YDGKAWLHIC VTGDDKNATA SIIYDGMLVD SIGSWSKNIL RTQESECVCI NGTCAVVMTD GSASGKADTR VLFIREGKII NISPLSGSAQ HVEECSCYPR YPEVRCVCRD NWKGSNRPIL YINMADYSIE SSYVCSGLVG DTPRNDDSSS SSNCRDPNNE RGAPGVKGWA FDDGNDVWMG RTIKNGSRSG YETFRVVNGW TMANSKSQIN RQVIVDSDDW SGYSGIFSVE GKKCINRCFY VELIRGRPQE PRVWWTSNSI IVFCGTSGTY GTGSWPDGAN INFMPI //