ID E1TZ58_9INFA Unreviewed; 466 AA. AC E1TZ58; DT 30-NOV-2010, integrated into UniProtKB/TrEMBL. DT 30-NOV-2010, sequence version 1. DT 11-DEC-2019, entry version 50. DE RecName: Full=Neuraminidase {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00397549}; DE EC=3.2.1.18 {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00397416}; GN Name=NA {ECO:0000256|HAMAP-Rule:MF_04071, GN ECO:0000256|RuleBase:RU361252, ECO:0000313|EMBL:ADO21050.1}; OS Influenza A virus (A/swine/Guangxi/10/2007(H9N2)). OC Viruses; Riboviria; Negarnaviricota; Polyploviricotina; Insthoviricetes; OC Articulavirales; Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=892007 {ECO:0000313|EMBL:ADO21050.1, ECO:0000313|Proteomes:UP000127919}; RN [1] {ECO:0000313|EMBL:ADO21050.1, ECO:0000313|Proteomes:UP000127919} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=A/swine/Guangxi/10/2007 {ECO:0000313|EMBL:ADO21050.1}; RA Yu H., Zhou Y.-J., Li G.-X., Tong G.-Z.; RT "Genetic diversity of H9N2 influenza viruses from pigs in China: a RT potential threat to human health?"; RL Submitted (SEP-2010) 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 ECO:0000256|SAAS:SAAS01126145}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000256|HAMAP-Rule:MF_04071, CC ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00612833}; 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 ECO:0000256|SAAS:SAAS01070481}. CC -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_04071, CC ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00397177}. CC -!- SUBCELLULAR LOCATION: Host apical cell membrane {ECO:0000256|HAMAP- CC Rule:MF_04071, ECO:0000256|SAAS:SAAS00582107}; Single-pass type II CC membrane protein {ECO:0000256|HAMAP-Rule:MF_04071, CC ECO:0000256|SAAS:SAAS00582107}. Virion membrane {ECO:0000256|HAMAP- CC Rule:MF_04071}. Note=Preferentially accumulates at the apical plasma CC membrane in infected polarized epithelial cells, which is the virus CC assembly site. Uses lipid rafts for cell surface transport and apical CC sorting. In the virion, forms a mushroom-shaped spike on the surface of CC 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 ECO:0000256|SAAS:SAAS00582269}. 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; CY075056; ADO21050.1; -; Viral_cRNA. DR CAZy; GH34; Glycoside Hydrolase Family 34. DR Proteomes; UP000127919; Genome. 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|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, KW ECO:0000256|SAAS:SAAS00474703}; KW Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|SAAS:SAAS00474860}; KW Glycoprotein {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252}; KW Glycosidase {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00474810}; KW Host cell membrane {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00474912}; KW Host membrane {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00475059}; KW Hydrolase {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, KW ECO:0000256|SAAS:SAAS00475017}; KW Membrane {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|SAAS:SAAS00474571}; KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00474602}; KW Signal-anchor {ECO:0000256|HAMAP-Rule:MF_04071}; KW Transmembrane {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|SAAS:SAAS00474655}; KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|SAAS:SAAS00475130}; KW Virion {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, KW ECO:0000256|SAAS:SAAS00475258}. FT TRANSMEM 7..30 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 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; 51242 MW; CFAF80D50130FC21 CRC64; MNPNQKIIAI GSVSLTIATI CFLMQIAILA TTMTLHFKQN ECSNPSNNQV VPCEPTIIER NIVHLNSTTI EKEICPKVAE YKNWSKPQCQ ITGSAPFSKG NSIRLSAGGD IWVTREPYVS CSLGKCYQFA LGQGTTLKNK HSNGTTHDRG PHRTLLMSEL GVPFHLGTKQ VCIAWSSSSC HDGKAWLHVC VTGDDKNATA SIIYDGMLVD SIGSWSKNIL RTQESECVCI NGTCTVVMTD GSASGKADTR ILFIREGKIV HISPLSGSAQ HVEECSCYPR YPEVRCVCRD NWKGSNRPVL YINMADYSIE SSYVCSGLVG DTPRNDDSYS SSNCRDPNNE SGAPGVKGWA FDNGNDIWMG RTIKEDSRSG YETFRVVGGW TTANSKSQIN RQVIVDSDNW SGYSGIFSVE GKNCINRCFY VELIRGRPQE TRVWWTSNSI IVFCGTSGTY GTGSWPDGAN INFMPI //