NRAM_I02A1
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 03-AUG-2022, entry version 79.
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 genotype
OS X0).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
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., 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).
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.
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;
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 -!- 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.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000250}. Host apical cell
CC membrane {ECO:0000250}; Single-pass type II membrane protein
CC {ECO:0000250}. Note=Preferentially accumulates at the apical plasma
CC membrane in infected polarized epithelial cells, which is the virus
CC assembly site. Uses lipid rafts for cell surface transport and apical
CC sorting. In the virion, forms a mushroom-shaped spike on the surface of
CC the membrane (By similarity). {ECO:0000250}.
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 (By
CC 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 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. {ECO:0000305}.
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DR EMBL; AY651457; AAT73339.1; -; Genomic_RNA.
DR SMR; 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 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; Disulfide bond; Glycoprotein; Glycosidase; Host cell membrane;
KW Host membrane; Hydrolase; Membrane; Metal-binding; Signal-anchor;
KW Transmembrane; Transmembrane helix; Virion.
FT CHAIN 1..>358
FT /note="Neuraminidase"
FT /id="PRO_0000310934"
FT TOPO_DOM 1..6
FT /note="Intravirion"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..>358
FT /note="Virion surface"
FT /evidence="ECO:0000255"
FT REGION 11..33
FT /note="Involved in apical transport and lipid raft
FT association"
FT /evidence="ECO:0000250"
FT REGION 36..70
FT /note="Hypervariable stalk region"
FT /evidence="ECO:0000250"
FT REGION 71..>358
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000250"
FT ACT_SITE 131
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 132
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 257..258
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 273
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 274
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 278
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 304
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 348
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 104..109
FT /evidence="ECO:0000250"
FT DISULFID 164..211
FT /evidence="ECO:0000250"
FT DISULFID 213..218
FT /evidence="ECO:0000250"
FT DISULFID 259..272
FT /evidence="ECO:0000250"
FT DISULFID 261..270
FT /evidence="ECO:0000250"
FT DISULFID 298..315
FT /evidence="ECO:0000250"
FT NON_TER 358
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
