NRAM_I71A2
ID NRAM_I71A2 Reviewed; 469 AA.
AC P03476; Q05JI0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 116.
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/Turkey/Oregon/1971 H7N3).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=385636;
OH NCBI_TaxID=8782; Aves.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Kida H., Sakoda Y.;
RT "Establishment of gene library of all haemagglutinin (HA) and neuraminidase
RT (NA) subtypes for the control of influenza A virus infection.";
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-94.
RX PubMed=6896994; DOI=10.1021/bi00260a015;
RA Blok J., Air G.M.;
RT "Variation in the membrane-insertion and 'stalk' sequences in eight
RT subtypes of influenza type A virus neuraminidase.";
RL Biochemistry 21:4001-4007(1982).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-94.
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 NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=17121796; DOI=10.1128/jvi.01667-06;
RA Cauthen A.N., Swayne D.E., Sekellick M.J., Marcus P.I., Suarez D.L.;
RT "Amelioration of influenza virus pathogenesis in chickens attributed to the
RT enhanced interferon-inducing capacity of a virus with a truncated NS1
RT gene.";
RL J. Virol. 81:1838-1847(2007).
RN [5]
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 [6]
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 [7]
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}.
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DR EMBL; AB276110; BAF34372.1; -; Genomic_RNA.
DR EMBL; V01092; CAA24276.1; -; Genomic_RNA.
DR EMBL; K01011; AAA43361.1; -; Genomic_RNA.
DR EMBL; DQ870890; ABH04381.1; -; Genomic_RNA.
DR EMBL; DQ870896; ABH04387.1; -; Genomic_RNA.
DR SMR; P03476; -.
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-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 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; 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..469
FT /note="Neuraminidase"
FT /id="PRO_0000078719"
FT TOPO_DOM 1..6
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT TRANSMEM 7..29
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT TOPO_DOM 30..469
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..469
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 405
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 278..279
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 BINDING 298
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 324
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 370
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 92..416
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 124..129
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
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 280..292
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 282..290
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 318..336
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 420..447
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CONFLICT 94
FT /note="F -> S (in Ref. 2; CAA24276 and 3; AAA43361)"
SQ SEQUENCE 469 AA; 51790 MW; 1758078B2ABE0F65 CRC64;
MNPNQKIITI GVVNTTLSTI ALLIGVGNLV FNTVIHEKIG NHQTVIHPTI TTPAVPNCSD
TIITYNNTVI NNITTTIITE AERLFKPPLP LCPFRGFFPF HKDNAIRLGE NKDVIVTREP
YVSCDNDNCW SFALAQGALL GTKHSNGTIK DRTPYRSLIR FPIGTAPVLG NYKEICIAWS
SSSCFDGKEW MHVCMTGNDN DASAQIIYAG RMTDSIKSWR KDILRTQESE CQCIGGTCVV
AVTDGPAANS ADHRVYWIRE GRIVKYENVP KTKIQHLEEC SCYVDIDVYC ICRDNWKGSN
RPWMRINNET ILETGYVCSK FHSDTPRPAD PSTVSCDSPS NINGGPGVKG FGFKAGNDVW
LGRTVSTSGR SGFEIIKVTD GWINSPNHAK SVTQTLVSNN DWSGYSGSFI VKTKGCFQPC
FYVELIRGRP NKNDDVSWTS NSIVTFCGLD NEPGSGNWPD GSNIGFMPK
