NRAM_I68A3
ID NRAM_I68A3 Reviewed; 470 AA.
AC P03477; Q6XV48;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 120.
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/Ontario/6118/1968 H8N4).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=311175;
OH NCBI_TaxID=8782; Aves.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Webby R.J., Humberd J.L., Krauss S.L.;
RT "Genetic analysis of multiple N3, N4, and N6 influenza A virus
RT neuraminidase genes.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
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].
RA Tanaka Y., 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 (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-79.
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 [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; AY207528; AAO62042.1; -; Genomic_RNA.
DR EMBL; CY014660; ABI84520.1; -; Genomic_RNA.
DR EMBL; AB289344; BAF43469.1; -; Genomic_RNA.
DR EMBL; K01013; AAA43364.1; -; Genomic_RNA.
DR EMBL; V01093; CAA24277.1; -; Genomic_RNA.
DR SMR; P03477; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR PRO; PR:P03477; -.
DR Proteomes; UP000007770; Genome.
DR Proteomes; UP000131583; 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 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..470
FT /note="Neuraminidase"
FT /id="PRO_0000078718"
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..470
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 90..470
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 150
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 117
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 276..277
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 292
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 293
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 297
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 323
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 50
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine; by host"
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 62
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 145
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 269
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 CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 91..418
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 123..128
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 183..230
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 232..237
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 278..291
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 280..289
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 317..334
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 422..447
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CONFLICT 25
FT /note="Q -> P (in Ref. 4; AAA43364/CAA24277)"
FT CONFLICT 40
FT /note="V -> G (in Ref. 4; AAA43364/CAA24277)"
FT CONFLICT 50..56
FT /note="NNTTNYY -> TTQRITI (in Ref. 4; AAA43364/CAA24277)"
FT CONFLICT 75..78
FT /note="EPSA -> DPQP (in Ref. 4; AAA43364/CAA24277)"
SQ SEQUENCE 470 AA; 51891 MW; B9292CA549C98C30 CRC64;
MNPNQKIITI GSASIVLTTI GLLLQITSLC SIWFSHYNQV TQPHEQACSN NTTNYYNETF
VNVTNVQNNY TTIIEPSAPN VVHYSSGRDL CPVKGWAPLS KDNGIRIGSR GEVFVIREPF
ISCSISECRT FFLTQGALLN DKHSNGTVKD RSPFRTLMSC PMGVAPSPSN SRFESVAWSA
TACSDGPGWL TLGITGPDAT AVAVLKYNGI ITDTLKSWKG NIMRTQESEC VCQDEFCYTL
ITDGPSNAQA FYKILKIRKG KIVSVKDVNA TGFHFEECSC YPSGTDVECV CRDNWRGSNR
PWIRFNSDLD YQIGYVCSGI FGDNPRPVDG IGSCNSPVNN GKGRYGVKGF SFRYGDGVWI
GRTKSLESRS GFEMVWDANG WVSTDKDSNG VQDIIDNNNW SGYSGSFSIR WETTGRNCTV
PCFWVEMIRG QPKEKTIWTS GSSIAFCGVN SDTTGWSWPD GALLPFDIDK
