NRAM_I18A0
ID NRAM_I18A0 Reviewed; 469 AA.
AC Q9IGQ6; O10421;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 113.
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/Brevig Mission/1/1918 H1N1) (Influenza A virus
OS (strain A/South Carolina/1/1918 H1N1)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=88776;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10823895; DOI=10.1073/pnas.100140097;
RA Reid A.H., Fanning T.G., Janczewski T.A., Taubenberger J.K.;
RT "Characterization of the 1918 'Spanish' influenza virus neuraminidase
RT gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6785-6790(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 12-23.
RC STRAIN=A/South Carolina/1/18;
RX PubMed=9065404; DOI=10.1126/science.275.5307.1793;
RA Taubenberger J.K., Reid A.H., Krafft A.E., Bijwaard K.E., Fanning T.G.;
RT "Initial genetic characterization of the 1918 'Spanish' influenza virus.";
RL Science 275:1793-1796(1997).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 83-467 IN COMPLEX WITH CALCIUM
RP AND INHIBITOR ZANAMIVIR, COFACTOR, SUBUNIT, GLYCOSYLATION AT ASN-146, AND
RP DISULFIDE BOND.
RX PubMed=18715929; DOI=10.1128/jvi.00959-08;
RA Xu X., Zhu X., Dwek R.A., Stevens J., Wilson I.A.;
RT "Structural characterization of the 1918 influenza virus H1N1
RT neuraminidase.";
RL J. Virol. 82:10493-10501(2008).
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 -!- 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 Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:18715929};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04071,
CC ECO:0000269|PubMed:18715929};
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 ECO:0000269|PubMed:18715929}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04071}. Host apical cell membrane {ECO:0000255|HAMAP-
CC Rule:MF_04071}; Single-pass type II membrane protein
CC {ECO:0000255|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:0000255|HAMAP-
CC 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 ECO:0000269|PubMed:18715929}.
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 -!- MISCELLANEOUS: South Carolina isolate has been sequenced from formalid
CC fixed-lung tissues of a 21-year-old male which died in 1918 at Ft.
CC Jackson, SC. Brevig Mission isolate has been sequenced from lung
CC tissues of an Inuit woman buried in the permafrost in a gravesite near
CC Brevig Mission, Alaska. This sample was recovered by John Hultin,
CC retired pathologist.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family.
CC {ECO:0000255|HAMAP-Rule:MF_04071}.
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DR EMBL; AF250356; AAF77036.1; -; mRNA.
DR EMBL; U94893; AAC57065.1; -; Genomic_DNA.
DR PDB; 3B7E; X-ray; 1.45 A; A/B=83-467.
DR PDB; 3BEQ; X-ray; 1.64 A; A/B=83-467.
DR PDB; 3CYE; X-ray; 1.65 A; A/B=83-469.
DR PDB; 6D96; X-ray; 2.15 A; A/B/C/D/E/F/G/H=82-469.
DR PDB; 6LXI; X-ray; 2.50 A; A/B=1-469.
DR PDBsum; 3B7E; -.
DR PDBsum; 3BEQ; -.
DR PDBsum; 3CYE; -.
DR PDBsum; 6D96; -.
DR PDBsum; 6LXI; -.
DR SMR; Q9IGQ6; -.
DR BindingDB; Q9IGQ6; -.
DR ChEMBL; CHEMBL1795169; -.
DR DrugCentral; Q9IGQ6; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR iPTMnet; Q9IGQ6; -.
DR BRENDA; 3.2.1.18; 7479.
DR SABIO-RK; Q9IGQ6; -.
DR EvolutionaryTrace; Q9IGQ6; -.
DR PRO; PR:Q9IGQ6; -.
DR Proteomes; UP000008430; 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 1: Evidence at protein level;
KW 3D-structure; Calcium; Disulfide bond; Glycoprotein; Glycosidase;
KW Host cell membrane; Host membrane; Hydrolase; Membrane; Metal-binding;
KW Signal-anchor; Transmembrane; Transmembrane helix; Virion.
FT CHAIN 1..469
FT /note="Neuraminidase"
FT /id="PRO_0000310569"
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..469
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..90
FT /note="Hypervariable stalk region"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 91..469
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 151
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 402
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 118
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 152
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 277..278
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 293
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 294
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT BINDING 298
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT BINDING 324
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT BINDING 344
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT BINDING 368
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 50
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 92..417
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT DISULFID 124..129
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT DISULFID 184..231
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT DISULFID 233..238
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT DISULFID 279..292
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT DISULFID 281..290
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT DISULFID 318..335
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT DISULFID 421..446
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:18715929"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:3B7E"
FT HELIX 105..109
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 115..124
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 129..142
FT /evidence="ECO:0007829|PDB:3B7E"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:3B7E"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 157..162
FT /evidence="ECO:0007829|PDB:3B7E"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 173..177
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 190..197
FT /evidence="ECO:0007829|PDB:3B7E"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:6LXI"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 211..217
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 237..245
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 252..259
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 262..268
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 277..284
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 287..293
FT /evidence="ECO:0007829|PDB:3B7E"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:6D96"
FT STRAND 302..306
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 312..316
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 356..361
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 365..376
FT /evidence="ECO:0007829|PDB:3B7E"
FT TURN 377..381
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 388..399
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 403..408
FT /evidence="ECO:0007829|PDB:3B7E"
FT HELIX 410..413
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 416..429
FT /evidence="ECO:0007829|PDB:3B7E"
FT TURN 430..432
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 433..436
FT /evidence="ECO:0007829|PDB:3B7E"
FT STRAND 438..450
FT /evidence="ECO:0007829|PDB:3B7E"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:6LXI"
SQ SEQUENCE 469 AA; 51406 MW; 28888692D4394159 CRC64;
MNPNQKIITI GSICMVVGII SLILQIGNII SIWVSHSIQT GNQNHPETCN QSIITYENNT
WVNQTYVNIS NTNVVAGQDA TSVILTGNSS LCPISGWAIY SKDNGIRIGS KGDVFVIREP
FISCSHLECR TFFLTQGALL NDKHSNGTVK DRSPYRTLMS CPVGEAPSPY NSRFESVAWS
ASACHDGMGW LTIGISGPDN GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT
IMTDGPSNGQ ASYKILKIEK GKVTKSIELN APNYHYEECS CYPDTGKVMC VCRDNWHGSN
RPWVSFDQNL DYQIGYICSG VFGDNPRPND GTGSCGPVSS NGANGIKGFS FRYDNGVWIG
RTKSTSSRSG FEMIWDPNGW TETDSSFSVR QDIVAITDWS GYSGSFVQHP ELTGLDCMRP
CFWVELIRGQ PKENTIWTSG SSISFCGVNS DTVGWSWPDG AELPFSIDK
