NRAM_I33A0
ID NRAM_I33A0 Reviewed; 453 AA.
AC P03470; Q67215; Q67216; Q67217;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Neuraminidase {ECO:0000255|HAMAP-Rule:MF_04071};
DE EC=3.2.1.18 {ECO:0000255|HAMAP-Rule:MF_04071};
GN Name=NA {ECO:0000255|HAMAP-Rule:MF_04071};
OS Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus
OS (strain A/WS/1933 H1N1)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=381518;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=A/WSN/33;
RX PubMed=7077751; DOI=10.1128/jvi.41.2.730-734.1982;
RA Hiti A.L., Nayak D.P.;
RT "Complete nucleotide sequence of the neuraminidase gene of human influenza
RT virus A/WSN/33.";
RL J. Virol. 41:730-734(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=A/NWS/33, A/WS/33, and A/WSN/33;
RX PubMed=8560787; DOI=10.1007/bf01701815;
RA Ward A.C.;
RT "Changes in the neuraminidase of neurovirulent influenza virus strains.";
RL Virus Genes 10:253-260(1995).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=10864667; DOI=10.1128/jvi.74.14.6538-6545.2000;
RA Barman S., Nayak D.P.;
RT "Analysis of the transmembrane domain of influenza virus neuraminidase, a
RT type II transmembrane glycoprotein, for apical sorting and raft
RT association.";
RL J. Virol. 74:6538-6545(2000).
RN [4]
RP FUNCTION.
RC STRAIN=A/WSN/33;
RX PubMed=16140748; DOI=10.1128/jvi.79.18.11705-11715.2005;
RA Suzuki T., Takahashi T., Guo C.T., Hidari K.I., Miyamoto D., Goto H.,
RA Kawaoka Y., Suzuki Y.;
RT "Sialidase activity of influenza A virus in an endocytic pathway enhances
RT viral replication.";
RL J. Virol. 79:11705-11715(2005).
RN [5]
RP REVIEW.
RX PubMed=15567494; DOI=10.1016/j.virusres.2004.08.012;
RA Nayak D.P., Hui E.K., Barman S.;
RT "Assembly and budding of influenza virus.";
RL Virus Res. 106:147-165(2004).
RN [6]
RP REVIEW.
RX PubMed=16192481; DOI=10.1056/nejmra050740;
RA Moscona A.;
RT "Neuraminidase inhibitors for influenza.";
RL N. Engl. J. Med. 353:1363-1373(2005).
RN [7]
RP REVIEW.
RX PubMed=15744059; DOI=10.1248/bpb.28.399;
RA Suzuki Y.;
RT "Sialobiology of influenza: molecular mechanism of host range variation of
RT influenza viruses.";
RL Biol. Pharm. Bull. 28:399-408(2005).
CC -!- FUNCTION: Unlike other strains, A/WSN/33 neuraminidase binds and
CC activates plasminogen into plasmin in the vicinity of HA so that
CC activated plasmin cleaves HA rendering the virus infectious.
CC {ECO:0000269|PubMed:16140748}.
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 moieties 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:0000255|HAMAP-Rule:MF_04071,
CC ECO:0000269|PubMed:16140748}.
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:0000255|HAMAP-
CC Rule:MF_04071};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04071};
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:0000255|HAMAP-Rule:MF_04071}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_04071}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-Rule:MF_04071,
CC ECO:0000269|PubMed:10864667}. Host apical cell membrane
CC {ECO:0000255|HAMAP-Rule:MF_04071, ECO:0000269|PubMed:10864667}; Single-
CC pass type II membrane protein {ECO:0000255|HAMAP-Rule:MF_04071,
CC ECO:0000269|PubMed:10864667}. 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:0000255|HAMAP-Rule:MF_04071}.
CC -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis.
CC Possesses 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:0000255|HAMAP-Rule:MF_04071}.
CC -!- PTM: N-glycosylated. {ECO:0000255|HAMAP-Rule:MF_04071}.
CC -!- MISCELLANEOUS: The influenza A genome consist of 8 RNA segments.
CC Genetic variation of hemagglutinin and/or neuraminidase genes results
CC in the emergence of new influenza strains. The mechanism of variation
CC can be the result of point mutations or the result of genetic
CC reassortment between segments of two different strains.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family.
CC {ECO:0000255|HAMAP-Rule:MF_04071}.
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DR EMBL; J02177; AAA43397.1; ALT_SEQ; Genomic_RNA.
DR EMBL; L25815; AAA91326.1; -; mRNA.
DR EMBL; L25816; AAA91327.1; -; mRNA.
DR EMBL; L25817; AAA91328.1; -; mRNA.
DR SMR; P03470; -.
DR BindingDB; P03470; -.
DR ChEMBL; CHEMBL1287610; -.
DR DrugCentral; P03470; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR PRO; PR:P03470; -.
DR Proteomes; UP000000834; 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:InterPro.
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 2: Evidence at transcript level;
KW Calcium; Disulfide bond; Glycoprotein; Glycosidase; Host cell membrane;
KW Host membrane; Hydrolase; Membrane; Metal-binding; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix; Virion.
FT CHAIN 1..453
FT /note="Neuraminidase"
FT /id="PRO_0000078726"
FT TOPO_DOM 1..6
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT TOPO_DOM 28..453
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 11..33
FT /note="Involved in apical transport and lipid raft
FT association"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 36..74
FT /note="Hypervariable stalk region"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 75..453
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 135
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 386
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 136
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 261..262
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 278
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 282
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 308
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 328
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 352
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 76..401
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 108..113
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 168..215
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 217..222
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 263..276
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 265..274
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 302..319
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 405..430
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT VARIANT 53
FT /note="I -> S (in strain: A/WSN/33)"
FT VARIANT 56..57
FT /note="YN -> HK (in strain: A/NWS/33)"
FT VARIANT 57
FT /note="N -> K (in strain: A/WSN/33)"
FT VARIANT 130
FT /note="N -> R (in strain: A/WSN/33)"
FT VARIANT 130
FT /note="N -> Y (in strain: A/NWS/33)"
FT VARIANT 133
FT /note="V -> F (in strain: A/WSN/33)"
FT VARIANT 133
FT /note="V -> S (in strain: A/NWS/33)"
FT VARIANT 184
FT /note="N -> D (in strain: A/WSN/33)"
FT VARIANT 206
FT /note="K -> N (in strain: A/WSN/33)"
FT VARIANT 232
FT /note="N -> D (in strain: A/WSN/33 and A/NWS/33)"
FT VARIANT 297
FT /note="Q -> K (in strain: A/WSN/33)"
FT VARIANT 316
FT /note="P -> T (in strain: A/WSN/33 and A/NWS/33)"
FT VARIANT 336
FT /note="R -> K (in strain: A/WSN/33)"
FT VARIANT 373
FT /note="V -> M (in strain: A/WSN/33)"
FT VARIANT 414
FT /note="R -> L (in strain: A/WSN/33)"
FT VARIANT 414
FT /note="R -> Q (in strain: A/NWS/33)"
FT VARIANT 418..419
FT /note="ET -> DA (in strain: A/WSN/33)"
FT VARIANT 434
FT /note="S -> G (in strain: A/WSN/33)"
FT CONFLICT 172
FT /note="M -> V (in Ref. 1; AAA43397)"
FT CONFLICT 380..382
FT /note="MTD -> ITN (in Ref. 1; AAA43397)"
SQ SEQUENCE 453 AA; 49687 MW; 76E63E3A97D1EFEC CRC64;
MNPNQKIITI GSICMVVGII SLILQIGNII SIWISHSIQT GNQNHTGICN QGIITYNVVA
GQDSTSVILT GNSSLCPIRG WAIHSKDNGI RIGSKGDVFV IREPFISCSH LECRTFFLTQ
GALLNDKHSN GTVKDRSPYR ALMSCPVGEA PSPYNSRFES VAWSASACHD GMGWLTIGIS
GPDNGAVAVL KYNGIITETI KSWRKKILRT QESECTCVNG SCFTIMTDGP SNGLASYKIF
KIEKGKVTKS IELNAPNSHY EECSCYPDTG KVMCVCRDNW HGSNRPWVSF DQNLDYQIGY
ICSGVFGDNP RPKDGPGSCG PVSADGANGV KGFSYRYGNG VWIGRTKSDS SRHGFEMIWD
PNGWTETDSR FSVRQDVVAM TDRSGYSGSF VQHPELTGLD CMRPCFWVEL IRGRPEEETI
WTSGSIISFC GVNSDTVDWS WPDGAELPFT IDK
