ID   D0VTW9_9INFA            Unreviewed;       470 AA.
AC   D0VTW9;
DT   15-DEC-2009, integrated into UniProtKB/TrEMBL.
DT   15-DEC-2009, sequence version 1.
DT   11-DEC-2019, entry version 54.
DE   RecName: Full=Neuraminidase {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00397549};
DE            EC=3.2.1.18 {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00397416};
GN   Name=NA {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252,
GN   ECO:0000313|EMBL:ACY01449.1};
OS   Influenza A virus (A/Esfahan/708/2008(H1N1)).
OC   Viruses; Riboviria; Negarnaviricota; Polyploviricotina; Insthoviricetes;
OC   Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=684568 {ECO:0000313|EMBL:ACY01449.1};
RN   [1] {ECO:0000313|EMBL:ACY01449.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=A/Esfahan/708/2008 {ECO:0000313|EMBL:ACY01449.1};
RA   Shafiei Jandaghi N.Z., Mokhtari Azad T.;
RT   "Molecular characterization and phylogenetic analysis of Iranian seasonal
RT   H1N1 influenza viruses from 2005 to 2009 and pandemic H1N1 compared with
RT   their corresponding vaccine strains.";
RL   Submitted (OCT-2009) 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         ECO:0000256|SAAS:SAAS01126145};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000256|HAMAP-Rule:MF_04071,
CC         ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00612833};
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       ECO:0000256|SAAS:SAAS01070481}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_04071,
CC       ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00397177}.
CC   -!- SUBCELLULAR LOCATION: Host apical cell membrane {ECO:0000256|HAMAP-
CC       Rule:MF_04071, ECO:0000256|SAAS:SAAS00582107}; Single-pass type II
CC       membrane protein {ECO:0000256|HAMAP-Rule:MF_04071,
CC       ECO:0000256|SAAS:SAAS00582107}. Virion membrane {ECO:0000256|HAMAP-
CC       Rule:MF_04071}. Note=Preferentially accumulates at the apical plasma
CC       membrane in infected polarized epithelial cells, which is the virus
CC       assembly site. Uses lipid rafts for cell surface transport and apical
CC       sorting. In the virion, forms a mushroom-shaped spike on the surface of
CC       the membrane. {ECO:0000256|HAMAP-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       ECO:0000256|SAAS:SAAS00582269}.
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; GU112240; ACY01449.1; -; Viral_cRNA.
DR   CAZy; GH34; Glycoside Hydrolase Family 34.
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:UniProtKB-UniRule.
DR   GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule.
DR   CDD; cd15483; Influenza_NA; 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; SSF50939; 1.
PE   3: Inferred from homology;
KW   Calcium {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252,
KW   ECO:0000256|SAAS:SAAS00474703};
KW   Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|SAAS:SAAS00474860};
KW   Glycoprotein {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|RuleBase:RU361252};
KW   Glycosidase {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00474810};
KW   Host cell membrane {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00474912};
KW   Host membrane {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00474912};
KW   Hydrolase {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252,
KW   ECO:0000256|SAAS:SAAS00474810};
KW   Membrane {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252,
KW   ECO:0000256|SAAS:SAAS00474912, ECO:0000256|SAAS:SAAS00475130};
KW   Metal-binding {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00474602};
KW   Signal-anchor {ECO:0000256|HAMAP-Rule:MF_04071};
KW   Transmembrane {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|SAAS:SAAS00475130};
KW   Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|SAAS:SAAS00475130};
KW   Virion {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252,
KW   ECO:0000256|SAAS:SAAS00475258}.
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          91..470
FT                   /note="Head of neuraminidase"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   REGION          277..278
FT                   /note="Substrate binding"
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        402
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   METAL           294
FT                   /note="Calcium; via carbonyl oxygen"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   METAL           298
FT                   /note="Calcium; via carbonyl oxygen"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   METAL           324
FT                   /note="Calcium"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   METAL           344
FT                   /note="Calcium; via carbonyl oxygen"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         118
FT                   /note="Substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         152
FT                   /note="Substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         293
FT                   /note="Substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   BINDING         368
FT                   /note="Substrate"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   DISULFID        92..417
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"
FT   DISULFID        318..335
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
SQ   SEQUENCE   470 AA;  51702 MW;  A0DE4674A26046FD CRC64;
     MNPNQKIITI GSISIAIGII SLMLQIGNII SIWASHSIQT GSQNNTGICN QRIITYENST
     WVNHTYVNIN NTNVVAGEDK TSVTLAGNSS LCSISGWAIY TKDNSIRIGS KGDVFVIREP
     FISCSHLECR TFFLTQGALL NDKHSNGTVK DRSPYRALMS CPLGEAPSPY NSKFESVAWS
     ASACHDGMGW LTIGISGPDN GAVAVLKYNG IITGTIKSWK KQILRTQESE CVCMNGSCFT
     IMTDGPSNKA ASYKIFKIEK GKVTKSIELN APNFHYEECS CYPDTGIVMC VCRDNWHGSN
     RPWVSFNQNL DYQIGYICSG VFGDNPRPED GEGSCNPVTV DGANGVKGFS YKYDNGVWIG
     RTKSNRLRKG FEMIWDPNGW TNTDSDFSVK QDVVAITDWS GYSGSFVQHP ELTGLDCIRP
     CFWVELVRGL PRENTTIWTS GSSISFCGVN SDTANWSWPD GAELPFIIDK
//