Legends: 1, ACT_SITE Proton donor/acceptor. {ECO:0000250}; 2, Calcium; via carbonyl oxygen. {ECO:0000250}; 3, Calcium. {ECO:0000250}; 4, BINDING Substrate. {ECO:0000250}; 5, N-linked (GlcNAc...); by host. {ECO:0000255}; 6, TOPO_DOM Intravirion. {ECO:0000255}; 7, TRANSMEM Helical. {ECO:0000255}; 8, REGION Involved in apical transport and lipid raft association. {ECO:0000250}; 9, REGION Hypervariable stalk region. {ECO:0000250}; 10, REGION Substrate binding. {ECO:0000250}.
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ID NRAM_I02A1 Reviewed; 358 AA.
AC Q6DPK2;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 24-JUN-2015, entry version 63.
DE RecName: Full=Neuraminidase;
DE EC=3.2.1.18;
DE Flags: Fragment;
GN Name=NA;
OS Influenza A virus (strain A/Guinea fowl/Hong Kong/38/2002 H5N1
OS genotype X0).
OC Viruses; ssRNA viruses; ssRNA negative-strand viruses;
OC Orthomyxoviridae; Influenzavirus A.
OX NCBI_TaxID=284208;
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.,
RA Rahardjo A.P., Puthavathana P., Buranathai C., Nguyen T.D.,
RA Estoepangestie A.T.S., Chaisingh A., Auewarakul P., Long H.T.,
RA Hanh N.T.H., Webby R.J., Poon L.L.M., Chen H., Shortridge K.F.,
RA Yuen K.Y., Webster R.G., Peiris J.S.M.;
RT "Genesis of a highly pathogenic and potentially pandemic H5N1
RT influenza virus in eastern Asia.";
RL Nature 430:209-213(2004).
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.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of alpha-(2->3)-, alpha-(2->6)-,
CC alpha-(2->8)- glycosidic linkages of terminal sialic acid residues
CC in oligosaccharides, glycoproteins, glycolipids, colominic acid
CC and synthetic substrates.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250};
CC -!- ENZYME 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.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000250}. Host apical
CC cell membrane {ECO:0000250}; Single-pass type II membrane protein
CC {ECO:0000250}. Note=Preferentially accumulates at the apical
CC plasma membrane in infected polarized epithelial cells, which is
CC the virus assembly site. Uses lipid rafts for cell surface
CC transport and apical sorting. In the virion, forms a mushroom-
CC shaped spike on the surface of the membrane (By similarity).
CC {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: The influenza A genome consist of 8 RNA segments.
CC Genetic variation of hemagglutinin and/or neuraminidase genes
CC results in the emergence of new influenza strains. The mechanism
CC of variation can be the result of point mutations or the result of
CC genetic reassortment between segments of two different strains.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family.
CC {ECO:0000305}.
DR EMBL; AY651457; AAT73339.1; -; Genomic_RNA.
DR ProteinModelPortal; Q6DPK2; -.
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 Gene3D; 2.120.10.10; -; 1.
DR InterPro; IPR001860; Glyco_hydro_34.
DR InterPro; IPR011040; Sialidases.
DR Pfam; PF00064; Neur; 1.
DR SUPFAM; SSF50939; SSF50939; 1.
PE 3: Inferred from homology;
KW 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 >358 Neuraminidase.
FT /FTId=PRO_0000310934.
FT TOPO_DOM 1 6 Intravirion. {ECO:0000255}.
FT TRANSMEM 7 27 Helical. {ECO:0000255}.
FT TOPO_DOM 28 >358 Virion surface. {ECO:0000255}.
FT REGION 11 33 Involved in apical transport and lipid
FT raft association. {ECO:0000250}.
FT REGION 36 70 Hypervariable stalk region.
FT {ECO:0000250}.
FT REGION 71 >358 Head of neuraminidase. {ECO:0000250}.
FT REGION 257 258 Substrate binding. {ECO:0000250}.
FT ACT_SITE 131 131 Proton donor/acceptor. {ECO:0000250}.
FT METAL 274 274 Calcium; via carbonyl oxygen.
FT {ECO:0000250}.
FT METAL 278 278 Calcium; via carbonyl oxygen.
FT {ECO:0000250}.
FT METAL 304 304 Calcium. {ECO:0000250}.
FT BINDING 98 98 Substrate. {ECO:0000250}.
FT BINDING 132 132 Substrate. {ECO:0000250}.
FT BINDING 273 273 Substrate. {ECO:0000250}.
FT BINDING 348 348 Substrate. {ECO:0000250}.
FT CARBOHYD 68 68 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 126 126 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT CARBOHYD 215 215 N-linked (GlcNAc...); by host.
FT {ECO:0000255}.
FT DISULFID 104 109 {ECO:0000250}.
FT DISULFID 164 211 {ECO:0000250}.
FT DISULFID 213 218 {ECO:0000250}.
FT DISULFID 259 272 {ECO:0000250}.
FT DISULFID 261 270 {ECO:0000250}.
FT DISULFID 298 315 {ECO:0000250}.
FT NON_TER 358 358
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 92 353 ipfam:Neur [T]
SQ SEQUENCE 358 AA; 39066 MW; 14EB44BF919407C6 CRC64;
MNPNRKIITI GSICMVIGIV SLMLQIGNII SIWVSHSIQT ENQHQAEPIS NTNFLTEKAV
ASVTLAGNSS LCPISGWAIH SKDNGIRIGS KGDVFVIREP FISCSHLECR TFFLTQGALL
NDKHSNGTVK DRSPHRTLMS CPVGEAPSPY NSRFESVAWS ASACHDGTSW LTIGISGPDN
GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT VMTDGPSNGQ ASYKIFKMEK
GKVVKSVELD APNYHYEECS CYPDAGEVTC VCRDNWHGSN RPWVSFNQNL EYQIGYICSG
VFGDNPRPND GTGSCGPMSL NGAYGVKGFS FKYGNGVWIG RTKSTNSRSG FEMIWDPN
//
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