ID F2NZA9_9INFA Unreviewed; 470 AA. AC F2NZA9; DT 31-MAY-2011, integrated into UniProtKB/TrEMBL. DT 31-MAY-2011, sequence version 1. DT 10-APR-2019, entry version 46. DE RecName: Full=Neuraminidase {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00114532}; DE EC=3.2.1.18 {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00114514}; 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; ssRNA viruses; ssRNA negative-strand viruses; OC Negarnaviricota; Polyploviricotina; Insthoviricetes; Articulavirales; OC 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., RA Tai H., 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 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:SAAS00114476}. 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; CY087279; ADZ53101.1; -; 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:SAAS00114513}; KW Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|SAAS:SAAS00114594}; 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:SAAS00114535}; KW Host cell membrane {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00114522}; KW Host membrane {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00114565}; KW Hydrolase {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00114491}; KW Membrane {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|SAAS:SAAS00114461}; KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00114385}; KW Signal-anchor {ECO:0000256|HAMAP-Rule:MF_04071}; KW Transmembrane {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|SAAS:SAAS00114524}; KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|SAAS:SAAS00114517}; KW Virion {ECO:0000256|HAMAP-Rule:MF_04071, KW ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00114362}. FT TRANSMEM 7 34 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 91 470 Head of neuraminidase. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT REGION 277 278 Substrate binding. {ECO:0000256|HAMAP- FT Rule:MF_04071}. FT ACT_SITE 151 151 Proton donor/acceptor. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT ACT_SITE 402 402 Nucleophile. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT METAL 294 294 Calcium; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT METAL 298 298 Calcium; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT METAL 324 324 Calcium. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT METAL 344 344 Calcium; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT BINDING 118 118 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 152 152 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 293 293 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 368 368 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT DISULFID 92 417 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 124 129 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 184 231 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 233 238 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 279 292 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 281 290 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 318 335 {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 //