ID A0A291IDB7_9INFA Unreviewed; 459 AA. AC A0A291IDB7; DT 20-DEC-2017, integrated into UniProtKB/TrEMBL. DT 20-DEC-2017, sequence version 1. DT 10-APR-2019, entry version 11. 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:ATG88194.1}; OS Influenza A virus (A/poultry/China/XY01.6/2016(H5N6)). OC Viruses; ssRNA viruses; ssRNA negative-strand viruses; OC Negarnaviricota; Polyploviricotina; Insthoviricetes; Articulavirales; OC Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=2042253 {ECO:0000313|EMBL:ATG88194.1}; RN [1] {ECO:0000313|EMBL:ATG88194.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/poultry/China/XY01.6/2016 {ECO:0000313|EMBL:ATG88194.1}; RA Zhao Z.; RT "Avian Influenza H5N6 Viruses Exhibit Differing Pathogenicity RT Pathogenicities and Transmissibilities in Mammals."; RL Sci. Rep. 0:0-0(2017). 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; MG029173; ATG88194.1; -; 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 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 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 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 80 459 Head of neuraminidase. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT REGION 266 267 Substrate binding. {ECO:0000256|HAMAP- FT Rule:MF_04071}. FT ACT_SITE 140 140 Proton donor/acceptor. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT ACT_SITE 395 395 Nucleophile. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT METAL 283 283 Calcium; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT METAL 287 287 Calcium; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_04071}. FT METAL 314 314 Calcium. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 107 107 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 141 141 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 282 282 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT BINDING 361 361 Substrate. {ECO:0000256|HAMAP-Rule: FT MF_04071}. FT DISULFID 113 118 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 173 220 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 222 227 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 268 281 {ECO:0000256|HAMAP-Rule:MF_04071}. FT DISULFID 270 279 {ECO:0000256|HAMAP-Rule:MF_04071}. SQ SEQUENCE 459 AA; 50744 MW; A942739EE62FE77D CRC64; MNPNQKITCI SATGVTLSVV SLLIGITNLG LNIGLHYKVS DSTTMNIPNM NETNPTTTNI TNIVMNKNEE RTFLKLTKPL CEVNSWHILS KDNAIRIGED AHILVTREPY LSCDPQGCRM FALSQGTTLR GQHANGTIHD RSPFRALISW EMGQAPSPYN TRAECIGWSS TSCHDGISRM SICISGPNNN ASAVVWYRGR PVTEIPSWAG NILRTQESEC VCHKGICPVV MTDGPANSKA ATKIIYFKEG KIQKTEELQG NAQHIEECSC YGAARMIKCV CRDNWKGANR PIITIDPEMM THTSKYLCSK ILTDTSRPND PTNGNCDAPI TGGSPDPGVK GFAFLDGENS WLGRTISKDS RSGYEMLKVP NAEIDTQSGP ISYQLIVNNQ NWSGYSGAFI DYWANKECFN PCFYVELIRG RPKESGVLWT SNSMVALCGS RERLGSWSWH DGAEIIYFK //