NRAM_I97A1
ID NRAM_I97A1 Reviewed; 450 AA.
AC Q9W7Y7; O89527; Q9WA99;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 113.
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/Hong Kong/156/1997 H5N1 genotype Gs/Gd).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=130763;
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 [MRNA].
RX PubMed=9482438; DOI=10.1016/s0140-6736(97)11212-0;
RA Claas E.C.J., Osterhaus A.D., van Beek R., De Jong J.C., Rimmelzwaan G.F.,
RA Senne D.A., Krauss S., Shortridge K.F., Webster R.G.;
RT "Human influenza A H5N1 virus related to a highly pathogenic avian
RT influenza virus.";
RL Lancet 351:472-477(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=9430591; DOI=10.1126/science.279.5349.393;
RA Subbarao K., Klimov A., Katz J., Regnery H., Lim W., Hall H., Perdue M.,
RA Swayne D., Bender C., Huang J., Hemphill M., Rowe T., Shaw M., Xu X.,
RA Fukuda K., Cox N.;
RT "Characterization of an avian influenza A (H5N1) virus isolated from a
RT child with a fatal respiratory illness.";
RL Science 279:393-396(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=9658115; DOI=10.1128/jvi.72.8.6678-6688.1998;
RA Suarez D.L., Perdue M.L., Cox N., Rowe T., Bender C., Huang J.,
RA Swayne D.E.;
RT "Comparisons of highly virulent H5N1 influenza A viruses isolated from
RT humans and chickens from Hong Kong.";
RL J. Virol. 72:6678-6688(1998).
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).
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC34264.1; Type=Erroneous initiation;
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DR EMBL; AF028708; AAC40507.1; -; mRNA.
DR EMBL; AF036357; AAC34264.1; ALT_INIT; Genomic_RNA.
DR EMBL; AF046089; AAC32089.1; -; Genomic_RNA.
DR SMR; Q9W7Y7; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR Proteomes; UP000008587; Genome.
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:InterPro.
DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule.
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 2: Evidence at transcript level;
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..450
FT /note="Neuraminidase"
FT /id="PRO_0000078700"
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..450
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..71
FT /note="Hypervariable stalk region"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 72..450
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 132
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 383
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 133
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 258..259
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 274
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 275
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
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 305
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 349
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 73..398
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 105..110
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 165..212
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 214..219
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 260..273
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 262..271
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 299..316
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 402..427
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CONFLICT 441..443
FT /note="GAD -> DAE (in Ref. 2; AAC34264)"
FT CONFLICT 443
FT /note="D -> E (in Ref. 3; AAC32089)"
SQ SEQUENCE 450 AA; 49503 MW; 0DCB54FCB6E7C8F2 CRC64;
MNPNQKIITI GSICMVVGII SLMLQIGNII SVWVSHIIQT WHPNQPEPCN QSINFYTEQA
AASVTLAGNS SLCPISGWAI YSKDNSIRIG SKGDVFVIRE PFISCSHLEC RTFFLTQGAL
LNDKHSNGTV KDRSPYRTLM SCPVGEAPSP YNSRFESVAW SASACHDGIS WLTIGISGPD
NGAVAVLKYN GIITDTIKSW RNNILRTQES ECACVNGSCF TVMTDGPSNE QASYKIFKIE
KGRVVKSVEL NAPNYHYEEC SCYPDAGEIT CVCRDNWHGS NRPWVSFNQN LEYQIGYICS
GVFGDSPRPN DGTGSCGPVS LNGAYGVKGF SFKYGNGVWI GRTKSTSSRS GFEMIWDPNG
WTETDSSFSL KQDIIAITDW SGYSGSFIQH PELTGLNCMR PCFWVELIRG RPKEKTIWTS
GSSISFCGVN SDTVGWSWPD GADLPFTIDK
