ID NRAM_I56A2 Reviewed; 470 AA. AC Q6XV27; Q83982; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 27-MAR-2024, entry version 103. DE RecName: Full=Neuraminidase {ECO:0000255|HAMAP-Rule:MF_04071}; DE EC=3.2.1.18 {ECO:0000255|HAMAP-Rule:MF_04071}; GN Name=NA {ECO:0000255|HAMAP-Rule:MF_04071}; OS Influenza A virus (strain A/Duck/England/1/1956 H11N6). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=383550; OH NCBI_TaxID=8782; Aves. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RA Webby R.J., Humberd J.L., Krauss S.L.; RT "Genetic analysis of multiple N3, N4, and N6 influenza A virus RT neuraminidase genes."; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=16439620; DOI=10.1126/science.1121586; RA Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., Finkelstein D.B., RA Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., Webster R.G., Hoffmann E., RA Krauss S., Zheng J., Zhang Z., Naeve C.W.; RT "Large-scale sequence analysis of avian influenza isolates."; RL Science 311:1576-1580(2006). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-71. RX PubMed=6927853; DOI=10.1016/0042-6822(82)90162-3; RA Blok J., Air G.M.; RT "Sequence variation at the 3' end of the neuraminidase gene from 39 RT influenza type A viruses."; RL Virology 121:211-229(1982). RN [4] RP REVIEW. RX PubMed=15567494; DOI=10.1016/j.virusres.2004.08.012; RA Nayak D.P., Hui E.K., Barman S.; RT "Assembly and budding of influenza virus."; RL Virus Res. 106:147-165(2004). RN [5] RP REVIEW. RX PubMed=16192481; DOI=10.1056/nejmra050740; RA Moscona A.; RT "Neuraminidase inhibitors for influenza."; RL N. Engl. J. Med. 353:1363-1373(2005). RN [6] RP REVIEW. RX PubMed=15744059; DOI=10.1248/bpb.28.399; RA Suzuki Y.; RT "Sialobiology of influenza: molecular mechanism of host range variation of RT influenza viruses."; RL Biol. Pharm. Bull. 28:399-408(2005). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 82-470 IN COMPLEX WITH CALCIUM RP AND SUBSTRATE ANALOG, COFACTOR, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION RP AT ASN-86; ASN-146 AND ASN-201. RA Rudino-Pinera E., Crennell S.J., Webster R.G., Laver W.G., Garman E.F.; RT "The crystal structure of influenza type A virus neuraminidase of the N6 RT subtype at 1.85 A resolution."; RL Submitted (APR-2004) to the PDB data bank. RN [8] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 82-470 IN COMPLEX WITH CALCIUM RP AND ZANAMIVIR, COFACTOR, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT RP ASN-146. RA Rudino-Pinera E., Tunnah P., Crennell S.J., Webster R.G., Laver W.G., RA Garman E.F.; RT "The crystal structure of type A influenza virus neuraminidase of the N6 RT subtype reveals the existence of two separate Neu5Ac binding sites."; RL Submitted (MAY-2006) to the PDB data bank. 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 moieties 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:0000255|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:0000255|HAMAP- CC Rule:MF_04071}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|HAMAP- CC Rule:MF_04071, ECO:0000269|Ref.7, ECO:0000269|Ref.8}; CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|Ref.7, CC ECO:0000269|Ref.8}; 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:0000255|HAMAP-Rule:MF_04071}. CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_04071, CC ECO:0000305|Ref.7, ECO:0000305|Ref.8}. CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP- CC Rule:MF_04071}. Host apical cell membrane {ECO:0000255|HAMAP- CC Rule:MF_04071}; Single-pass type II membrane protein CC {ECO:0000255|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:0000255|HAMAP- CC Rule:MF_04071}. CC -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis. CC Possesses 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:0000255|HAMAP-Rule:MF_04071}. CC -!- PTM: N-glycosylated. {ECO:0000255|HAMAP-Rule:MF_04071, CC ECO:0000269|Ref.7, ECO:0000269|Ref.8}. CC -!- MISCELLANEOUS: The influenza A genome consist of 8 RNA segments. CC Genetic variation of hemagglutinin and/or neuraminidase genes results CC in the emergence of new influenza strains. The mechanism of variation CC can be the result of point mutations or the result of genetic CC reassortment between segments of two different strains. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family. CC {ECO:0000255|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; AY207549; AAO62063.1; -; Genomic_DNA. DR EMBL; AB288846; BAF43436.1; -; Genomic_RNA. DR EMBL; CY014681; ABI84548.1; -; Genomic_RNA. DR EMBL; K01039; AAA43389.1; -; Genomic_RNA. DR PDB; 1V0Z; X-ray; 1.84 A; A/B/C/D=82-470. DR PDB; 1W1X; X-ray; 2.00 A; A/B/C/D=82-470. DR PDB; 1W20; X-ray; 2.08 A; A/B/C/D=82-470. DR PDB; 1W21; X-ray; 2.08 A; A/B/C/D=82-470. DR PDB; 2CML; X-ray; 2.15 A; A/B/C/D=82-470. DR PDB; 6HFY; X-ray; 1.65 A; A/B/C/D=82-470. DR PDB; 6HG5; X-ray; 1.60 A; A/B/C/D=82-470. DR PDB; 6HGB; X-ray; 1.50 A; A/B/C/D=82-470. DR PDBsum; 1V0Z; -. DR PDBsum; 1W1X; -. DR PDBsum; 1W20; -. DR PDBsum; 1W21; -. DR PDBsum; 2CML; -. DR PDBsum; 6HFY; -. DR PDBsum; 6HG5; -. DR PDBsum; 6HGB; -. DR SMR; Q6XV27; -. DR CAZy; GH34; Glycoside Hydrolase Family 34. DR GlyCosmos; Q6XV27; 9 sites, No reported glycans. DR EvolutionaryTrace; Q6XV27; -. DR PRO; PR:Q6XV27; -. DR Proteomes; UP000155465; Genome. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C: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:InterPro. DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule. DR Gene3D; 2.120.10.10; -; 1. 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; Sialidases; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Disulfide bond; Glycoprotein; Glycosidase; KW Host cell membrane; Host membrane; Hydrolase; Membrane; Metal-binding; KW Signal-anchor; Transmembrane; Transmembrane helix; Virion. FT CHAIN 1..470 FT /note="Neuraminidase" FT /id="PRO_0000280127" FT TOPO_DOM 1..6 FT /note="Intravirion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT TRANSMEM 7..27 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT TOPO_DOM 28..470 FT /note="Virion surface" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 11..33 FT /note="Involved in apical transport and lipid raft FT association" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 36..88 FT /note="Hypervariable stalk region" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 91..470 FT /note="Head of neuraminidase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 151 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 406 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 118 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 152 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 277..278 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 293 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 294 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|Ref.7, ECO:0000269|Ref.8" FT BINDING 298 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|Ref.7, ECO:0000269|Ref.8" FT BINDING 325 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|Ref.7, ECO:0000269|Ref.8" FT BINDING 348 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|Ref.7, ECO:0000269|Ref.8" FT BINDING 372 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 51 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 54 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 62 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 67 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 70 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 86 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|Ref.7" FT CARBOHYD 146 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|Ref.7, ECO:0000269|Ref.8" FT CARBOHYD 201 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|Ref.7" FT CARBOHYD 402 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 92..419 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 124..129 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 176..194 FT DISULFID 184..231 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 233..238 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 279..292 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 281..290 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 319..337 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 423..449 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT STRAND 95..102 FT /evidence="ECO:0007829|PDB:6HGB" FT HELIX 105..109 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 115..125 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 128..142 FT /evidence="ECO:0007829|PDB:6HGB" FT HELIX 143..145 FT /evidence="ECO:0007829|PDB:6HGB" FT TURN 146..149 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 157..162 FT /evidence="ECO:0007829|PDB:6HGB" FT TURN 169..171 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 173..185 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 187..197 FT /evidence="ECO:0007829|PDB:6HGB" FT HELIX 199..201 FT /evidence="ECO:0007829|PDB:6HFY" FT STRAND 203..208 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 211..217 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 219..222 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 237..245 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 247..249 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 252..259 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 262..268 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 277..284 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 287..293 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 295..297 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 302..307 FT /evidence="ECO:0007829|PDB:6HGB" FT TURN 308..311 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 312..317 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 320..322 FT /evidence="ECO:0007829|PDB:2CML" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 337..339 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 362..365 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 367..379 FT /evidence="ECO:0007829|PDB:6HGB" FT TURN 381..385 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 392..403 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 407..410 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 415..420 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 423..431 FT /evidence="ECO:0007829|PDB:6HGB" FT TURN 432..434 FT /evidence="ECO:0007829|PDB:6HGB" FT STRAND 441..453 FT /evidence="ECO:0007829|PDB:6HGB" FT HELIX 466..469 FT /evidence="ECO:0007829|PDB:6HGB" SQ SEQUENCE 470 AA; 51470 MW; C3C30CB83D15E0E7 CRC64; MNPNQKIICI SATGMTLSVV SLLVGIANLG LNIGLHYKVG DTPNVNIPNV NGTNSTTTII NNNTQNNFTN ITNIIQSKGG ERTFLNLTKP LCEVNSWHIL SKDNAIRIGE DAHILVTREP YLSCDPQGCR MFALSQGTTL RGRHANGTIH DRSPFRALIS WEMGQAPSPY NTRVECIGWS STSCHDGMSR MSICMSGPNN NASAVVWYGG RPITEIPSWA GNILRTQESE CVCHKGVCPV VMTDGPANNR AATKIIYFKE GKIQKIEELA GNAQHIEECS CYGAGGVIKC ICRDNWKGAN RPVITIDPEM MTHTSKYLCS KVLTDTSRPN DPTNGNCDAP ITGGSPDPGV KGFAFLDGEN SWLGRTISKD SRSGYEMLKV PNAETDIQSG PISNQVIVNN QNWSGYSGAF IDYWANKECF NPCFYVELIR GRPKESSVLW TSNSIVALCG SKKRLGSWSW HDGAEIIYFE //