NRAM_I02A7
ID NRAM_I02A7 Reviewed; 454 AA.
AC Q6DPI6;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Neuraminidase {ECO:0000255|HAMAP-Rule:MF_04071};
DE EC=3.2.1.18 {ECO:0000255|HAMAP-Rule:MF_04071};
DE Flags: Fragment;
GN Name=NA {ECO:0000255|HAMAP-Rule:MF_04071};
OS Influenza A virus (strain A/Teal/China/2978.1/2002 H5N1 genotype W).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=284215;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9685; Felis catus (Cat) (Felis silvestris catus).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9691; Panthera pardus (Leopard) (Felis pardus).
OH NCBI_TaxID=9694; Panthera tigris (Tiger).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=15241415; DOI=10.1038/nature02746;
RA Li K.S., Guan Y., Wang J., Smith G.J.D., Xu K.M., Duan L., Rahardjo A.P.,
RA Puthavathana P., Buranathai C., Nguyen T.D., Estoepangestie A.T.S.,
RA Chaisingh A., Auewarakul P., Long H.T., Hanh N.T.H., Webby R.J.,
RA Poon L.L.M., Chen H., Shortridge K.F., Yuen K.Y., Webster R.G.,
RA Peiris J.S.M.;
RT "Genesis of a highly pathogenic and potentially pandemic H5N1 influenza
RT virus in eastern Asia.";
RL Nature 430:209-213(2004).
RN [2]
RP SEQUENCE REVISION.
RA Li K.S., Guan Y., Wang J., Smith G.J.D., Xu K.M., Duan L., Rahardjo A.P.,
RA Puthavathana P., Buranathai C., Nguyen T.D., Estoepangestie A.T.S.,
RA Chaisingh A., Auewarakul P., Long H.T., Hanh N.T.H., Lim W., Webby R.J.,
RA Poon L.L.M., Chen H., Shortridge K.F., Yuen K.Y., Webster R.G.,
RA Peiris J.S.M.;
RL Submitted (MAR-2008) 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 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;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04071};
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 -!- 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 -!- 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}.
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DR EMBL; AY651473; AAT73355.2; -; Genomic_RNA.
DR SMR; Q6DPI6; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IEA:UniProtKB-EC.
DR GO; GO:0052795; F:exo-alpha-(2->6)-sialidase activity; IEA:UniProtKB-EC.
DR GO; GO:0052796; F:exo-alpha-(2->8)-sialidase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:InterPro.
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; Disulfide bond; Glycoprotein; Glycosidase; Host cell membrane;
KW Host membrane; Hydrolase; Membrane; Metal-binding; Signal-anchor;
KW Transmembrane; Transmembrane helix; Virion.
FT CHAIN <1..454
FT /note="Neuraminidase"
FT /id="PRO_0000310940"
FT TRANSMEM <1..13
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 14..454
FT /note="Virion surface"
FT /evidence="ECO:0000255"
FT REGION 21..75
FT /note="Hypervariable stalk region"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 76..454
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 136
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 387
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 103
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 137
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 262..263
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 278
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 279
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 283
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 309
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 353
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 77..402
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 109..114
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 169..216
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 218..223
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 264..277
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 266..275
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 303..320
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 406..431
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT NON_TER 1
SQ SEQUENCE 454 AA; 49799 MW; 09163590DFA4E0F0 CRC64;
VIGIVSLMLQ IGNIISIWVS HSIQTGNQHQ AEPCIQSIIT YENNTWVNQT YVNISNTNFL
TEKTVASVTL AGNSSLCPIS GWAVYSKDNG IRIGSKGDVF VIREPFISCS HLECRTFFLT
QGALLNDKHS NGTVKDRSPH RTLMSCPVGE APSPYNSRFE SVAWSASACH DGTNWLTIGI
SGPDNGAVAV LKYNGIITDT IKSWRNNILR TQESECACVN GSCFTVMTDG PSNGQASYKI
FRIEKGKVVK SVELNAPNYH YEECSCYPDA GEITCVCRDN WHGSNRPWVS FNQNLEYQIG
YICSGIFGDN PRPNDGTGSC GPVSSNGAYG IKGFSYKYGN GVWIGRTKST NSRSGFEMIW
DPNGWTGTDS NFSVKQDIVA ITDWSGYSGS FVQHPELTGL DCIRPCFWVE LIRGRPKEST
IWTSGSSISF CGVNSDTVGW SWPDGAELPF TIDK
