ID   A0A0U2L0R6_9INFA        Unreviewed;       470 AA.
AC   A0A0U2L0R6;
DT   16-MAR-2016, integrated into UniProtKB/TrEMBL.
DT   16-MAR-2016, sequence version 1.
DT   29-MAY-2024, entry version 42.
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, ECO:0000313|EMBL:ALT66974.1};
OS   Influenza A virus (A/northern shoveler/Utah/A00468715/2009(H7N6)).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus;
OC   Alphainfluenzavirus influenzae; Influenza A virus.
OX   NCBI_TaxID=1769703 {ECO:0000313|EMBL:ALT66974.1};
RN   [1] {ECO:0000313|EMBL:ALT66974.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=A/northern shoveler/Utah/A00468715/2009
RC   {ECO:0000313|EMBL:ALT66974.1};
RX   PubMed=26858078; DOI=10.1038/srep20688;
RA   Xu Y., Bailey E., Spackman E., Li T., Wang H., Long L.P., Baroch J.A.,
RA   Cunningham F.L., Lin X., Jarman R.G., DeLiberto T.J., Wan X.F.;
RT   "Limited Antigenic Diversity in Contemporary H7 Avian-Origin Influenza A
RT   Viruses from North America.";
RL   Sci. Rep. 6:20688-20688(2016).
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,
CC         ECO:0000256|HAMAP-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; KU290296; ALT66974.1; -; Viral_cRNA.
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   Gene3D; 2.120.10.10; -; 1.
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; Sialidases; 1.
PE   3: Inferred from homology;
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|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252}.
FT   TRANSMEM        7..31
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..470
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         277..278
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         293
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         294
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         298
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         325
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         372
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        124..129
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        184..231
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        233..238
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        279..292
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        281..290
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
SQ   SEQUENCE   470 AA;  51741 MW;  1204528C0CB23896 CRC64;
     MNPNQKIICI SATGMTLSVV SLLIGLANLG LNIGLHFKVG DTPETEPPST NETNSTTTII
     NYNTQNNFTN VTNIVLIKEE NKMFTNLSKP LCEVNSWHIL SKDNAIRIGE NAHILVTREP
     YLSCGPHECR MFALSQGTTL RGRHANGTIH DRSPFRALIS WEMGQAPSPY NVRVECVGWS
     STSCHDGISR MSICMSGPNN NASAVVWYNG RPVTEIASWA GNILRTQESE CVCHNGICPV
     VMTDGPANNR AETKIIYFKE GKIQKIEELT GSAQHIEECS CYGAEEVIKC ICRDNWKGAN
     RPVITINPTT MTHTSKYLCS KILTDTSRPN DPGSGNCDAP ITGGSPDPGV KGFAFLDGGN
     SWLGRTISKD SRSGYEMLKV PNAETDNQSG PVAHQVIVNN QNWSGYSGAF IDYWADRECF
     NPCFYVELIR GRPKESSVLW TSNSIVALCG SRERLGSWSW HDGAEIIYFK
//