NRAM_I56A3
ID NRAM_I56A3 Reviewed; 469 AA.
AC P88838; Q20P40; Q83983;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 109.
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/Equine/Prague/1/1956 H7N7).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=380337;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9796; Equus caballus (Horse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9709; Phocidae (true seals).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9191869; DOI=10.1007/s007050050140;
RA Brown I.H., Hill M.L., Harris P.A., Alexander D.J., McCauley J.W.;
RT "Genetic characterisation of an influenza A virus of unusual subtype (H1N7)
RT isolated from pigs in England.";
RL Arch. Virol. 142:1045-1050(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=16439620; DOI=10.1126/science.1121586;
RA Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., Finkelstein D.B.,
RA Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., Webster R.G., Hoffmann E.,
RA Krauss S., Zheng J., Zhang Z., Naeve C.W.;
RT "Large-scale sequence analysis of avian influenza isolates.";
RL Science 311:1576-1580(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-88.
RA Blok J.;
RT "Sequence variation at the 3' end of the neuraminidase gene from 39
RT influenza type A viruses.";
RL (In) Nayak D., Fox C.F. (eds.);
RL Genetic variation among influenza viruses, pp.45-54, University of
RL California, Los Angeles (1982).
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}.
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DR EMBL; U85989; AAC57418.1; -; mRNA.
DR EMBL; CY005802; ABB20501.1; -; Genomic_RNA.
DR EMBL; K01008; AAA43411.1; -; Genomic_RNA.
DR SMR; P88838; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR PRIDE; P88838; -.
DR PRO; PR:P88838; -.
DR Proteomes; UP000121173; 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 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 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..469
FT /note="Neuraminidase"
FT /id="PRO_0000280138"
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..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..85
FT /note="Hypervariable stalk region"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 88..469
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 148
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 403
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 115
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 149
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 274..275
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 290
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 291
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 295
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 322
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 369
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 28
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 65
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 85
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 399
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 89..417
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 121..126
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 181..228
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 230..235
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 276..289
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 278..287
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 316..334
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 421..448
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CONFLICT 85
FT /note="N -> K (in Ref. 3; AAA43411)"
SQ SEQUENCE 469 AA; 51890 MW; 38A224BA86D9ADC8 CRC64;
MNPNQKLFAS SGIAIALGII NLLIGISNMS LNISLYSKGE NHKSDNLTCT NINQNNTTMV
NTYINNTTII DKNTKMENPG YLLLNKSLCN VEGWVVIAKD NAIRFGESEQ IIVTREPYVS
CDPLSCKMYA LHQGTTIRNK HSNGTTHDRT AFRGLISTPL GNPPTVSNSE FICVGWSSTS
CHDGVSRMTI CVQGNNENAT ATVYYNKRLT TTIKTWAKNI LRTQESECVC HNSTCVVVMT
DGPANNQAFT KVIYFHKGTI IKEEPLKGSA KHIEECSCYG HNQRVTCVCR DNWQGANRPV
IEIDMNNLEH TSRYICTGVL TDTSRPKDKA IGECFNPITG SPGAPGIKGF GFLNENNTWL
GRTISPKLRS GFEMLKIPNA GTDPDSKIKE RQEIVGNDNW SGYSGSFIDY WNDNSECYNP
CFYVELIRGR PEEAKYVEWT SNSLIALCGS PIPVGSGSFP DGAQIKYFS
