ID A0A0N7APG9_9INFA Unreviewed; 465 AA. AC A0A0N7APG9; DT 20-JAN-2016, integrated into UniProtKB/TrEMBL. DT 20-JAN-2016, sequence version 1. DT 05-JUN-2019, entry version 30. 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:AJU15324.1}; OS Influenza A virus (A/chicken/Huai'an/041/2014(H7N9)). OC Viruses; Riboviria; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; OC Alphainfluenzavirus. OX NCBI_TaxID=1621105 {ECO:0000313|EMBL:AJU15324.1}; RN [1] {ECO:0000313|EMBL:AJU15324.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/chicken/Huai'an/041/2014 {ECO:0000313|EMBL:AJU15324.1}; RA Chooi Y.-H.; RL Submitted (FEB-2015) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:AJU15324.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/chicken/Huai'an/041/2014 {ECO:0000313|EMBL:AJU15324.1}; RX PubMed=27927274; RA Yang P.F., Yan Q.L., Liu C.C., Xing Y.D., Zhang M.H., Gao Q., Yu H., RA Yao H.B., He N.J.; RT "Characterization of Avian Influenza A (H7N9) Virus Prevalence in RT Humans and Poultry in Huai'an, China: Molecular Epidemiology, RT Phylogenetic, and Dynamics Analyses."; RL Biomed. Environ. Sci. 29:742-753(2016). CC -!- FUNCTION: Catalyzes the removal of terminal sialic acid residues CC from viral and cellular glycoconjugates. Cleaves off the terminal CC sialic acids on the glycosylated HA during virus budding to CC facilitate virus release. Additionally helps virus spread through CC the circulation by further removing sialic acids from the cell CC surface. These cleavages prevent self-aggregation and ensure the CC efficient spread of the progeny virus from cell to cell. CC Otherwise, infection would be limited to one round of replication. CC Described as a receptor-destroying enzyme because it cleaves a CC terminal sialic acid from the cellular receptors. May facilitate CC viral invasion of the upper airways by cleaving the sialic acid CC moities on the mucin of the airway epithelial cells. Likely to CC plays a role in the budding process through its association with CC lipid rafts during intracellular transport. May additionally CC display a raft-association independent effect on budding. Plays a CC role in the determination of host range restriction on replication CC and virulence. Sialidase activity in late endosome/lysosome CC traffic seems to enhance virus replication. {ECO:0000256|HAMAP- CC Rule:MF_04071, ECO:0000256|SAAS:SAAS00844152}. 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:SAAS01116071}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000256|HAMAP- CC Rule:MF_04071, ECO:0000256|RuleBase:RU361252, CC ECO:0000256|SAAS:SAAS00612833}; CC -!- ACTIVITY REGULATION: Inhibited by the neuraminidase inhibitors CC zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs CC interfere with the release of progeny virus from infected cells CC and are effective against all influenza strains. Resistance to CC neuraminidase inhibitors is quite rare. {ECO:0000256|HAMAP- CC Rule:MF_04071, 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 CC {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|SAAS:SAAS00582107}; CC Single-pass type II membrane protein {ECO:0000256|HAMAP- CC Rule:MF_04071, ECO:0000256|SAAS:SAAS00582107}. Virion membrane CC {ECO:0000256|HAMAP-Rule:MF_04071}. Note=Preferentially accumulates CC at the apical plasma membrane in infected polarized epithelial CC cells, which is the virus assembly site. Uses lipid rafts for cell CC surface transport and apical sorting. In the virion, forms a CC mushroom-shaped spike on the surface of the membrane. CC {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 CC is likely to be a glycan, and the other in the transmembrane CC domain. The transmembrane domain also plays a role in lipid raft CC association. {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 CC of 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; KP864445; AJU15324.1; -; 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|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, 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, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00475017}; KW Membrane {ECO:0000256|HAMAP-Rule:MF_04071, KW 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, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00475258}. FT TRANSMEM 7 31 Helical. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT REGION 11 33 Involved in apical transport and lipid FT raft association. {ECO:0000256|HAMAP- FT Rule:MF_04071}. FT REGION 87 465 Head of neuraminidase. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT REGION 273 274 Substrate binding. {ECO:0000256|HAMAP- FT Rule:MF_04071}. FT ACT_SITE 147 147 Proton donor/acceptor. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT ACT_SITE 401 401 Nucleophile. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT METAL 290 290 Calcium; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT METAL 294 294 Calcium; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT METAL 321 321 Calcium. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT METAL 343 343 Calcium; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT BINDING 114 114 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 148 148 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 289 289 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 367 367 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT DISULFID 120 125 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 180 227 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 229 234 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 275 288 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 277 286 {ECO:0000256|HAMAP-Rule:MF_04071}. SQ SEQUENCE 465 AA; 51837 MW; C7F79B467E891604 CRC64; MNPNQKILCT SATAIIISAI AVLIGIANLG LNIGLHLKPG CNCSHSQPET TNTSQTIINN YYNETNITNI QMEERTSRNF NNLTKGLCTI NSWHIYGKDN AVRIGESSDV LVTREPYVSC DPDECRFYAL SQGTTIRGKH SNGTIHDRSQ YRALISWPLS SPPTVYNSRV ECIGWSSTSC HDGKSRMSIC ISGPNNNASA VVWYNRRPVA EINTWARNIL RTQESECVCH NGVCPVVFTD GSATGPADTR IYYFKEGKIL KWESLTGTAK HIEECSCYGE RTGITCTCRD NWQGSNRPVI QIDPVAMTHT SQYICSPVLT DTPRPNDPNI GKCNDPYPGN NNNGVKGFSY LDGANTWLGR TISTASRSGY EMLKVPNALT DDRSKPIQGQ TIVLNTDWSG YSGSFMDYWA EGDCYRACFY VELIRGRPKE DKVWWTSNSI VSMCSSTEFL GQWNWPDGAK IEYFL //