NRAM_I56A2
ID NRAM_I56A2 Reviewed; 470 AA.
AC Q6XV27; Q83982;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 97.
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/Duck/England/1/1956 H11N6).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=383550;
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] OF 1-71.
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 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).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 82-470 IN COMPLEX WITH CALCIUM
RP AND SUBSTRATE ANALOG, COFACTOR, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION
RP AT ASN-86; ASN-146 AND ASN-201.
RA Rudino-Pinera E., Crennell S.J., Webster R.G., Laver W.G., Garman E.F.;
RT "The crystal structure of influenza type A virus neuraminidase of the N6
RT subtype at 1.85 A resolution.";
RL Submitted (APR-2004) to the PDB data bank.
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 82-470 IN COMPLEX WITH CALCIUM
RP AND ZANAMIVIR, COFACTOR, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT
RP ASN-146.
RA Rudino-Pinera E., Tunnah P., Crennell S.J., Webster R.G., Laver W.G.,
RA Garman E.F.;
RT "The crystal structure of type A influenza virus neuraminidase of the N6
RT subtype reveals the existence of two separate Neu5Ac binding sites.";
RL Submitted (MAY-2006) to the PDB data bank.
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 Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|Ref.7,
CC ECO:0000269|Ref.8};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04071, ECO:0000269|Ref.7,
CC ECO:0000269|Ref.8};
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 ECO:0000305|Ref.7, ECO:0000305|Ref.8}.
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 ECO:0000269|Ref.7, ECO:0000269|Ref.8}.
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; AY207549; AAO62063.1; -; Genomic_DNA.
DR EMBL; AB288846; BAF43436.1; -; Genomic_RNA.
DR EMBL; CY014681; ABI84548.1; -; Genomic_RNA.
DR EMBL; K01039; AAA43389.1; -; Genomic_RNA.
DR PDB; 1V0Z; X-ray; 1.84 A; A/B/C/D=82-470.
DR PDB; 1W1X; X-ray; 2.00 A; A/B/C/D=82-470.
DR PDB; 1W20; X-ray; 2.08 A; A/B/C/D=82-470.
DR PDB; 1W21; X-ray; 2.08 A; A/B/C/D=82-470.
DR PDB; 2CML; X-ray; 2.15 A; A/B/C/D=82-470.
DR PDB; 6HFY; X-ray; 1.65 A; A/B/C/D=82-470.
DR PDB; 6HG5; X-ray; 1.60 A; A/B/C/D=82-470.
DR PDB; 6HGB; X-ray; 1.50 A; A/B/C/D=82-470.
DR PDBsum; 1V0Z; -.
DR PDBsum; 1W1X; -.
DR PDBsum; 1W20; -.
DR PDBsum; 1W21; -.
DR PDBsum; 2CML; -.
DR PDBsum; 6HFY; -.
DR PDBsum; 6HG5; -.
DR PDBsum; 6HGB; -.
DR SMR; Q6XV27; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR EvolutionaryTrace; Q6XV27; -.
DR PRO; PR:Q6XV27; -.
DR Proteomes; UP000155465; 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 1: Evidence at protein level;
KW 3D-structure; Calcium; Disulfide bond; Glycoprotein; Glycosidase;
KW Host cell membrane; Host membrane; Hydrolase; Membrane; Metal-binding;
KW Signal-anchor; Transmembrane; Transmembrane helix; Virion.
FT CHAIN 1..470
FT /note="Neuraminidase"
FT /id="PRO_0000280127"
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 91..470
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 406
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 277..278
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 ECO:0000269|Ref.7, ECO:0000269|Ref.8"
FT BINDING 298
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|Ref.7, ECO:0000269|Ref.8"
FT BINDING 325
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|Ref.7, ECO:0000269|Ref.8"
FT BINDING 348
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|Ref.7, ECO:0000269|Ref.8"
FT BINDING 372
FT /ligand="substrate"
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 54
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 67
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|Ref.7"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|Ref.7, ECO:0000269|Ref.8"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|Ref.7"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 92..419
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 124..129
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 176..194
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 279..292
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 281..290
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 319..337
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 423..449
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:6HGB"
FT HELIX 105..109
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 115..125
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 128..142
FT /evidence="ECO:0007829|PDB:6HGB"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:6HGB"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 157..162
FT /evidence="ECO:0007829|PDB:6HGB"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 173..185
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 187..197
FT /evidence="ECO:0007829|PDB:6HGB"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:6HFY"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 211..217
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 237..245
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 252..259
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 262..268
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 277..284
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 287..293
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 302..307
FT /evidence="ECO:0007829|PDB:6HGB"
FT TURN 308..311
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:2CML"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 367..379
FT /evidence="ECO:0007829|PDB:6HGB"
FT TURN 381..385
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 392..403
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 407..410
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 415..420
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 423..431
FT /evidence="ECO:0007829|PDB:6HGB"
FT TURN 432..434
FT /evidence="ECO:0007829|PDB:6HGB"
FT STRAND 441..453
FT /evidence="ECO:0007829|PDB:6HGB"
FT HELIX 466..469
FT /evidence="ECO:0007829|PDB:6HGB"
SQ SEQUENCE 470 AA; 51470 MW; C3C30CB83D15E0E7 CRC64;
MNPNQKIICI SATGMTLSVV SLLVGIANLG LNIGLHYKVG DTPNVNIPNV NGTNSTTTII
NNNTQNNFTN ITNIIQSKGG ERTFLNLTKP LCEVNSWHIL SKDNAIRIGE DAHILVTREP
YLSCDPQGCR MFALSQGTTL RGRHANGTIH DRSPFRALIS WEMGQAPSPY NTRVECIGWS
STSCHDGMSR MSICMSGPNN NASAVVWYGG RPITEIPSWA GNILRTQESE CVCHKGVCPV
VMTDGPANNR AATKIIYFKE GKIQKIEELA GNAQHIEECS CYGAGGVIKC ICRDNWKGAN
RPVITIDPEM MTHTSKYLCS KVLTDTSRPN DPTNGNCDAP ITGGSPDPGV KGFAFLDGEN
SWLGRTISKD SRSGYEMLKV PNAETDIQSG PISNQVIVNN QNWSGYSGAF IDYWANKECF
NPCFYVELIR GRPKESSVLW TSNSIVALCG SKKRLGSWSW HDGAEIIYFE
