ID   Q80DL0_9INFA            Unreviewed;       469 AA.
AC   Q80DL0;
DT   01-JUN-2003, integrated into UniProtKB/TrEMBL.
DT   01-JUN-2003, sequence version 1.
DT   27-MAR-2024, entry version 122.
DE   RecName: Full=Neuraminidase {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252};
DE            EC=3.2.1.18 {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252};
GN   Name=NA {ECO:0000256|HAMAP-Rule:MF_04071,
GN   ECO:0000256|RuleBase:RU361252};
OS   Influenza A virus (A/Memphis/31/98(H3N2)).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus;
OC   Alphainfluenzavirus influenzae; Influenza A virus.
OX   NCBI_TaxID=228928 {ECO:0000313|EMBL:AAP23239.1};
RN   [1] {ECO:0000313|EMBL:AAP23239.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=A/Memphis/31/98 {ECO:0000313|EMBL:AAP23239.1};
RX   PubMed=12414967; DOI=10.1128/JVI.76.23.12274-12280.2002;
RA   Gulati U., Hwang C.C., Venkatramani L., Gulati S., Stray S.J., Lee J.T.,
RA   Laver W.G., Bochkarev A., Zlotnick A., Air G.M.;
RT   "Antibody epitopes on the neuraminidase of a recent H3N2 influenza virus
RT   (A/Memphis/31/98).";
RL   J. Virol. 76:12274-12280(2002).
RN   [2] {ECO:0000313|EMBL:AAP23239.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=A/Memphis/31/98 {ECO:0000313|EMBL:AAP23239.1};
RA   Ren Z., Wang J., Chen J., Xiao Y., Zhang W., Sun D.;
RL   Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0007829|PDB:2AEQ}
RP   X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 75-469 IN COMPLEX WITH MANNOSE
RP   AND N-ACETYL-D-GLUCOSAMINE, AND DISULFIDE BONDS.
RX   PubMed=16384583; DOI=10.1016/j.jmb.2005.11.061;
RA   Venkatramani L., Bochkareva E., Lee J.T., Gulati U., Graeme Laver W.,
RA   Bochkarev A., Air G.M.;
RT   "An epidemiologically significant epitope of a 1998 human influenza virus
RT   neuraminidase forms a highly hydrated interface in the NA-antibody
RT   complex.";
RL   J. Mol. Biol. 356:651-663(2006).
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 moities 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:0000256|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:0000256|HAMAP-
CC         Rule:MF_04071, ECO:0000256|RuleBase:RU361252};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000256|ARBA:ARBA00001913, ECO:0000256|HAMAP-
CC         Rule:MF_04071, ECO:0000256|RuleBase:RU361252};
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:0000256|HAMAP-Rule:MF_04071}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000256|ARBA:ARBA00011881,
CC       ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004606}; Single-
CC       pass type II membrane protein {ECO:0000256|ARBA:ARBA00004606}. Virion
CC       membrane {ECO:0000256|HAMAP-Rule:MF_04071}. Host apical cell membrane
CC       {ECO:0000256|HAMAP-Rule:MF_04071}; Single-pass type II membrane protein
CC       {ECO:0000256|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:0000256|HAMAP-
CC       Rule:MF_04071}.
CC   -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis.
CC       Possess 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:0000256|HAMAP-Rule:MF_04071}.
CC   -!- PTM: N-glycosylated. {ECO:0000256|HAMAP-Rule:MF_04071,
CC       ECO:0000256|RuleBase:RU361252}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family.
CC       {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}.
CC   -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC       feature annotation. {ECO:0000256|HAMAP-Rule:MF_04071}.
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DR   EMBL; AY271795; AAP23239.1; -; Genomic_RNA.
DR   PDB; 2AEQ; X-ray; 3.00 A; A=75-469.
DR   PDBsum; 2AEQ; -.
DR   SMR; Q80DL0; -.
DR   CAZy; GH34; Glycoside Hydrolase Family 34.
DR   EvolutionaryTrace; Q80DL0; -.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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:UniProtKB-UniRule.
DR   GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule.
DR   CDD; cd15483; Influenza_NA; 1.
DR   Gene3D; 2.120.10.10; -; 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; Sialidases; 1.
PE   1: Evidence at protein level;
KW   3D-structure {ECO:0007829|PDB:2AEQ};
KW   Calcium {ECO:0000256|ARBA:ARBA00022837, ECO:0000256|HAMAP-Rule:MF_04071};
KW   Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04071};
KW   Glycoprotein {ECO:0000256|ARBA:ARBA00023180, ECO:0000256|HAMAP-
KW   Rule:MF_04071};
KW   Glycosidase {ECO:0000256|ARBA:ARBA00023295, ECO:0000256|HAMAP-
KW   Rule:MF_04071};
KW   Host cell membrane {ECO:0000256|ARBA:ARBA00022511, ECO:0000256|HAMAP-
KW   Rule:MF_04071};
KW   Host membrane {ECO:0000256|ARBA:ARBA00022870, ECO:0000256|HAMAP-
KW   Rule:MF_04071};
KW   Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|HAMAP-Rule:MF_04071};
KW   Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|HAMAP-Rule:MF_04071};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP-
KW   Rule:MF_04071};
KW   Signal-anchor {ECO:0000256|ARBA:ARBA00022968, ECO:0000256|HAMAP-
KW   Rule:MF_04071};
KW   Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|HAMAP-
KW   Rule:MF_04071};
KW   Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, ECO:0000256|HAMAP-
KW   Rule:MF_04071};
KW   Virion {ECO:0000256|ARBA:ARBA00022844, ECO:0000256|HAMAP-Rule:MF_04071}.
FT   TRANSMEM        12..37
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   REGION          11..33
FT                   /note="Involved in apical transport and lipid raft
FT                   association"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   REGION          91..469
FT                   /note="Head of neuraminidase"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   ACT_SITE        151
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   ACT_SITE        406
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         118
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         152
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         200
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   BINDING         234
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   BINDING         276..277
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         284
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   BINDING         292
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         293
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         297
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         324
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         371
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         393
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   BINDING         394
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   BINDING         454
FT                   /ligand="N-acetyl-D-glucosamine"
FT                   /ligand_id="ChEBI:CHEBI:506227"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   CARBOHYD        200
FT                   /note="N-acetyl-D-glucosamine 1"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   CARBOHYD        234
FT                   /note="N-acetyl-D-glucosamine 2"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   CARBOHYD        284
FT                   /note="N-acetyl-D-glucosamine 2"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   CARBOHYD        393
FT                   /note="N-acetyl-D-glucosamine 3"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   CARBOHYD        394
FT                   /note="N-acetyl-D-glucosamine 3"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   CARBOHYD        454
FT                   /note="N-acetyl-D-glucosamine 1"
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   DISULFID        92..417
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071,
FT                   ECO:0007829|PDB:2AEQ"
FT   DISULFID        124..129
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071,
FT                   ECO:0007829|PDB:2AEQ"
FT   DISULFID        175..193
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   DISULFID        183..230
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071,
FT                   ECO:0007829|PDB:2AEQ"
FT   DISULFID        232..237
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071,
FT                   ECO:0007829|PDB:2AEQ"
FT   DISULFID        278..291
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071,
FT                   ECO:0007829|PDB:2AEQ"
FT   DISULFID        280..289
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071,
FT                   ECO:0007829|PDB:2AEQ"
FT   DISULFID        318..337
FT                   /evidence="ECO:0007829|PDB:2AEQ"
FT   DISULFID        421..447
FT                   /evidence="ECO:0007829|PDB:2AEQ"
SQ   SEQUENCE   469 AA;  52110 MW;  46B453F12B0D2754 CRC64;
     MNPNQKIITI GSVSLTIATI CFLMQIAILV TTVTLHFKQY ECSSPPNNQV MLCEPTIIER
     NITEIVYLTN TTIEKEICPK LAEYRNWSKP QCKITGFAPF SKDNSIRLSA GGDIWVTREP
     YVSCDPDKCY QFALGQGTTL NNRHSNDTVH DRTPYRTLLM NELGVPFHLG TKQVCIAWSS
     SSCHDGKAWL HVCVTGHDEN ATASFIYDGR LVDSIGSWSK KILRTQESEC VCINGTCTVV
     MTDGSASGRA DTKILFIEEG KIVHISPLSG SAQHVEECSC YPRYPGVRCV CRDNWKGSNR
     PIVDINVKDY SIVSSYVCSG LVGDTPRKND SSSSSHCLNP NNEEGGHGVK GWAFDDGNDV
     WMGRTISEKF RSGYETFKVI EGWSKPNSKL QINRQVIVDR GNRSGYSGIF SVEGKSCINR
     CFYVELIRGR KQETEVWWTS NSIVVFCGTS GTYGTGSWPD GADINLMPI
//