ID   C6G5K0_9INFA            Unreviewed;       469 AA.
AC   C6G5K0;
DT   01-SEP-2009, integrated into UniProtKB/TrEMBL.
DT   01-SEP-2009, sequence version 1.
DT   02-JUN-2021, entry version 58.
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:ACL11973.1};
OS   Influenza A virus (A/chicken/Chakwal/NARC-35/2001(H7N3)).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=585042 {ECO:0000313|EMBL:ACL11973.1, ECO:0000313|Proteomes:UP000169326};
RN   [1] {ECO:0000313|EMBL:ACL11973.1, ECO:0000313|Proteomes:UP000169326}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=A/chicken/Chakwal/NARC-35/2001 {ECO:0000313|EMBL:ACL11973.1};
RX   PubMed=20576101;
RA   Abbas M.A., Spackman E., Swayne D.E., Ahmed Z., Sarmento L., Siddique N.,
RA   Naeem K., Hameed A., Rehmani S.;
RT   "Sequence and phylogenetic analysis of H7N3 avian influenza viruses
RT   isolated from poultry in Pakistan 1995-2004.";
RL   Virol. J. 7:137-137(2010).
RN   [2] {ECO:0000313|EMBL:ADI34039.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=A/chicken/Chakwal/NARC-35/2001 {ECO:0000313|EMBL:ADI34039.1};
RA   Abbas M.A., Spackman E., Ahmed Z., Naeem K., Siddique N., Swayne D.,
RA   Sarmento L., Hameed A.;
RT   "Studies on Biological Characteristics & Evaluation of Antigenic Drift in
RT   the Field Isolates of Avian Influenza Viruses.";
RL   Submitted (MAY-2010) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the removal of terminal sialic acid residues from
CC       viral and cellular glycoconjugates. {ECO:0000256|RuleBase:RU361252}.
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,
CC       ECO:0000256|RuleBase:RU361252}. Host apical cell membrane
CC       {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|RuleBase:RU361252};
CC       Single-pass type II membrane protein {ECO:0000256|HAMAP-Rule:MF_04071,
CC       ECO:0000256|RuleBase:RU361252}. Note=Preferentially accumulates at the
CC       apical plasma membrane in infected polarized epithelial cells, which is
CC       the virus assembly site. Uses lipid rafts for cell surface transport
CC       and apical sorting. In the virion, forms a mushroom-shaped spike on the
CC       surface of 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   -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC       feature annotation. {ECO:0000256|HAMAP-Rule:MF_04071}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; FJ577520; ACL11973.1; -; Viral_cRNA.
DR   EMBL; HM346487; ADI34039.1; -; Viral_cRNA.
DR   CAZy; GH34; Glycoside Hydrolase Family 34.
DR   Proteomes; UP000169326; 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:UniProtKB-UniRule.
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   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..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..469
FT                   /note="Head of neuraminidase"
FT                   /evidence="ECO:0000256|HAMAP-Rule:MF_04071"
FT   REGION          278..279
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        405
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   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         370
FT                   /note="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"
SQ   SEQUENCE   469 AA;  51877 MW;  6ECC8AAFFBC528A1 CRC64;
     MNPNQKIITI GVVNTTLSTI ALLIGIGNLV FNTVIHEKVG EQKTVAYPTV TSPVVPNCSD
     TIITYNSTVV NNITTTIVTE AERHFKSSLP LCPFRGFFPF HKDNAIRLGE NKDVIVTREP
     YVSCDYNDCW SFALAQGALL GTNHSNGTIK DRTPYRSLIR FPIGVAPVLG NYKEICVAWS
     SSSCFDGKEW MHVCMTGNDN DASAQIIYAG KMTDSIKSWR KDILRTQESE CQCIDGTCVV
     AVTDGPAANN ADHRIYWIRK GRVIKYENIP KTKIKHLEEC SCYVDIDVYC ICRDNWKGSN
     RPWMRINNET ILETGYVCSK FHSDTPRPDD PSTVSCDSPS NVNGGPGVKG FGFKTGNDVW
     LGRTVSNSGR SGFEIIKVTE GWINSPNHAK SVTQTLVSNN DWSGYSGSFI VESNGCFQPC
     FYIELIRGKP NKNDNVSWTS NSIVTFCGLD NEPGSGNWPD GSNIGFMPK
//