ID   B1MR93_9INFA            Unreviewed;       449 AA.
AC   B1MR93;
DT   29-APR-2008, integrated into UniProtKB/TrEMBL.
DT   29-APR-2008, sequence version 1.
DT   13-NOV-2019, entry version 67.
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,
GN   ECO:0000256|RuleBase:RU361252, ECO:0000313|EMBL:ACA48002.1};
OS   Influenza A virus (A/chicken/Yunnan/1083/2003(H5N1)).
OC   Viruses; Riboviria; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae;
OC   Alphainfluenzavirus.
OX   NCBI_TaxID=496744 {ECO:0000313|EMBL:ACA48002.1};
RN   [1] {ECO:0000313|EMBL:ACA48002.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=A/chicken/Yunnan/1083/2003 {ECO:0000313|EMBL:ACA48002.1};
RX   PubMed=18216109; DOI=10.1128/JVI.02468-07;
RA   Wang J., Vijaykrishna D., Duan L., Bahl J., Zhang J.X., Webster R.G.,
RA   Peiris J.S., Chen H., Smith G.J., Guan Y.;
RT   "Identification of the progenitors of Indonesian and Vietnamese avian
RT   influenza A (H5N1) viruses from southern China.";
RL   J. Virol. 82:3405-3414(2008).
CC   -!- FUNCTION: Catalyzes the removal of terminal sialic acid residues
CC       from viral and cellular glycoconjugates. Cleaves off the terminal
CC       sialic acids on the glycosylated HA during virus budding to
CC       facilitate virus release. Additionally helps virus spread through
CC       the circulation by further removing sialic acids from the cell
CC       surface. These cleavages prevent self-aggregation and ensure the
CC       efficient spread of the progeny virus from cell to cell.
CC       Otherwise, infection would be limited to one round of replication.
CC       Described as a receptor-destroying enzyme because it cleaves a
CC       terminal sialic acid from the cellular receptors. May facilitate
CC       viral invasion of the upper airways by cleaving the sialic acid
CC       moities on the mucin of the airway epithelial cells. Likely to
CC       plays a role in the budding process through its association with
CC       lipid rafts during intracellular transport. May additionally
CC       display a raft-association independent effect on budding. Plays a
CC       role in the determination of host range restriction on replication
CC       and virulence. Sialidase activity in late endosome/lysosome
CC       traffic seems to enhance virus replication. {ECO:0000256|HAMAP-
CC       Rule:MF_04071, ECO:0000256|SAAS:SAAS00844152}.
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; Evidence={ECO:0000256|HAMAP-
CC         Rule:MF_04071, ECO:0000256|RuleBase:RU361252,
CC         ECO:0000256|SAAS:SAAS00612833};
CC   -!- ACTIVITY REGULATION: Inhibited by the neuraminidase inhibitors
CC       zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs
CC       interfere with the release of progeny virus from infected cells
CC       and are effective against all influenza strains. Resistance to
CC       neuraminidase inhibitors is quite rare. {ECO:0000256|HAMAP-
CC       Rule:MF_04071, 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
CC       {ECO:0000256|HAMAP-Rule:MF_04071, ECO:0000256|SAAS:SAAS00582107};
CC       Single-pass type II membrane protein {ECO:0000256|HAMAP-
CC       Rule:MF_04071, ECO:0000256|SAAS:SAAS00582107}. Virion membrane
CC       {ECO:0000256|HAMAP-Rule:MF_04071}. Note=Preferentially accumulates
CC       at the apical plasma membrane in infected polarized epithelial
CC       cells, which is the virus assembly site. Uses lipid rafts for cell
CC       surface transport and apical sorting. In the virion, forms a
CC       mushroom-shaped spike on the surface of the membrane.
CC       {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
CC       is likely to be a glycan, and the other in the transmembrane
CC       domain. The transmembrane domain also plays a role in lipid raft
CC       association. {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
CC       of feature annotation. {ECO:0000256|HAMAP-Rule:MF_04071}.
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DR   EMBL; CY029379; ACA48002.1; -; 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,
KW   ECO:0000256|RuleBase:RU361252, 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:SAAS00475059};
KW   Hydrolase {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00475017};
KW   Membrane {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|SAAS:SAAS00474571};
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:SAAS00474655};
KW   Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|SAAS:SAAS00475130};
KW   Virion {ECO:0000256|HAMAP-Rule:MF_04071,
KW   ECO:0000256|RuleBase:RU361252, ECO:0000256|SAAS:SAAS00475258}.
FT   TRANSMEM      7     34       Helical. {ECO:0000256|HAMAP-Rule:
FT                                MF_04071}.
FT   REGION       11     33       Involved in apical transport and lipid
FT                                raft association. {ECO:0000256|HAMAP-
FT                                Rule:MF_04071}.
FT   REGION       71    449       Head of neuraminidase.
FT                                {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   REGION      257    258       Substrate binding. {ECO:0000256|HAMAP-
FT                                Rule:MF_04071}.
FT   ACT_SITE    131    131       Proton donor/acceptor.
FT                                {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   ACT_SITE    382    382       Nucleophile. {ECO:0000256|HAMAP-Rule:
FT                                MF_04071}.
FT   METAL       274    274       Calcium; via carbonyl oxygen.
FT                                {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   METAL       278    278       Calcium; via carbonyl oxygen.
FT                                {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   METAL       304    304       Calcium. {ECO:0000256|HAMAP-Rule:
FT                                MF_04071}.
FT   BINDING      98     98       Substrate. {ECO:0000256|HAMAP-Rule:
FT                                MF_04071}.
FT   BINDING     132    132       Substrate. {ECO:0000256|HAMAP-Rule:
FT                                MF_04071}.
FT   BINDING     273    273       Substrate. {ECO:0000256|HAMAP-Rule:
FT                                MF_04071}.
FT   BINDING     348    348       Substrate. {ECO:0000256|HAMAP-Rule:
FT                                MF_04071}.
FT   DISULFID     72    397       {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   DISULFID    104    109       {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   DISULFID    164    211       {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   DISULFID    213    218       {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   DISULFID    259    272       {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   DISULFID    261    270       {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   DISULFID    298    315       {ECO:0000256|HAMAP-Rule:MF_04071}.
FT   DISULFID    401    426       {ECO:0000256|HAMAP-Rule:MF_04071}.
SQ   SEQUENCE   449 AA;  48984 MW;  7D7EFE877FDE9CCD CRC64;
     MNPNQKIITI GSICMVTGIV SLMLQIGNMI SIWVSHSIHT GNQHQAEPIS NTNFLTEKAV
     ASVTLAGNSS LCPISGWAVH SKDNSIRIGS KGDVFVIREP FISCSHLECR TFFLTQGALL
     NDKHSNGTVK DRSPHRTLMS CPVGEAPSPY NSKFESVAWS ASACHDGTSW LTIGISGPDN
     GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT VMTDGPSNGQ ASYKIFKMEK
     GKVVKSVELD APNYHYEECS CYPDAGEITC VCRDNWHGSN RPWVSFNQNL EYQIGYICSG
     VFGDNPRPND GTGSCGPVSS NGAYGVKGFS FKYGNGVWIG RTKSTNSRSG FEMIWDPNGW
     TETDSSFSVK QDIVAITDWS GYSGSFVQHP ELTGLDCIRP CFWVELIRGR PKESTIWTSG
     SSISFCGVNS DTVGWSWPDG AELPFTIDK
//