ID   Q29SK8_9INFA            Unreviewed;       449 AA.
AC   Q29SK8;
DT   04-APR-2006, integrated into UniProtKB/TrEMBL.
DT   04-APR-2006, sequence version 1.
DT   27-MAR-2024, entry version 93.
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:AAX53526.1};
OS   Influenza A virus (A/chicken/Henan/210/2004(H5N1)).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus;
OC   Alphainfluenzavirus influenzae; Influenza A virus.
OX   NCBI_TaxID=319101 {ECO:0000313|EMBL:AAX53526.1};
RN   [1] {ECO:0000313|EMBL:AAX53526.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=A/Chicken/Henan/210/2004 {ECO:0000313|EMBL:AAX53526.1};
RA   Hu J., Chen Z., Zhang X., Yu J.;
RT   "A cohort of AIV H5N1 subtypes isolated from wild aquatic birds and
RT   domestic poultry revealed rapid transmission, frequent reassortment, and
RT   identifiable recombination events.";
RL   Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
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; AY950245; AAX53526.1; -; Genomic_RNA.
DR   SMR; Q29SK8; -.
DR   CAZy; GH34; Glycoside Hydrolase Family 34.
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   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|ARBA:ARBA00022844, ECO:0000256|HAMAP-Rule:MF_04071}.
FT   TRANSMEM        7..34
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          71..449
FT                   /note="Head of neuraminidase"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   ACT_SITE        131
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   ACT_SITE        382
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         98
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         132
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         257..258
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         273
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         274
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         278
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         304
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         348
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        72..397
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        104..109
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        164..211
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        213..218
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        259..272
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        261..270
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        298..315
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        401..426
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
SQ   SEQUENCE   449 AA;  48953 MW;  746A5DDA01B20713 CRC64;
     MNPNQKIITI GSICMVIGIV SLMLQIGNMI SIWVSHSIQT GNQHQAEPIS NTNFLTEKAV
     ASVTLAGNSS LCPISGWAVH SKDNSIRIGS KGDVFVIREP FISCSHLECR TFFLTQGALL
     NDKHSNGTVK DRSPHRTLMS CPVGEAPSPY NSRFESVAWS ASACHDGTSW LTIGISGPDN
     GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT VMTDGPSNGQ ASYKIFKMEK
     GKVVKSVELD APNYHYEECS CYPDAGEITC VCRDNWHGSN RPWVSFNQNL EYQIGYICSG
     VFGDNPRPND GTGSCGPVSP NGAYGVKGFS FKYGNGVWIG RTKSTNSRSG FEMIWDPNGW
     TGTDSSFSVK QDIVAITDWS GYSGSFVQHP ELTGLDCIRP CFWVELIRGR PKESTIWTSG
     SSISFCGVNS DTVGWSWPDG AELPFTIDK
//