NRAM_I84A1
ID NRAM_I84A1 Reviewed; 470 AA.
AC P05803;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 149.
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/Whale/Maine/1/1984 H13N9).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=11484;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9721; Cetacea (whales).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3660585; DOI=10.1016/0042-6822(87)90005-5;
RA Air G.M., Webster R.G., Colman P.M., Laver W.G.;
RT "Distribution of sequence differences in influenza N9 neuraminidase of tern
RT and whale viruses and crystallization of the whale neuraminidase complexed
RT with antibodies.";
RL Virology 160:346-354(1987).
RN [2]
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 [3]
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 [4]
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).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH CALCIUM; SUBSTRATE
RP ANALOG AND THE NC10 ANTIBODY, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION
RP AT ASN-87 AND ASN-147.
RX PubMed=7994573; DOI=10.1016/s0969-2126(00)00074-5;
RA Malby R.L., Tulip W.R., Harley V.R., McKimm-Breschkin J.L., Laver W.G.,
RA Webster R.G., Colman P.M.;
RT "The structure of a complex between the NC10 antibody and influenza virus
RT neuraminidase and comparison with the overlapping binding site of the NC41
RT antibody.";
RL Structure 2:733-746(1994).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 83-470 IN COMPLEX WITH ANTIBODIES
RP NC41 AND NC10, AND GLYCOSYLATION AT ASN-87 AND ASN-202.
RX PubMed=7517697; DOI=10.1021/bi00192a002;
RA Tulip W.R., Harley V.R., Webster R.G., Novotny J.;
RT "N9 neuraminidase complexes with antibodies NC41 and NC10: empirical free
RT energy calculations capture specificity trends observed with mutant binding
RT data.";
RL Biochemistry 33:7986-7997(1994).
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.;
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 ECO:0000269|PubMed:7517697, ECO:0000269|PubMed:7994573}.
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:7517697, ECO:0000269|PubMed:7994573}.
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; M17812; AAA43575.1; -; Genomic_RNA.
DR PDB; 1NCD; X-ray; 2.90 A; N=83-470.
DR PDB; 1NMA; X-ray; 3.00 A; N=83-470.
DR PDB; 1NMB; X-ray; 2.20 A; N=1-470.
DR PDB; 2B8H; X-ray; 2.20 A; A/B/C/D=83-470.
DR PDBsum; 1NCD; -.
DR PDBsum; 1NMA; -.
DR PDBsum; 1NMB; -.
DR PDBsum; 2B8H; -.
DR SMR; P05803; -.
DR MINT; P05803; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR iPTMnet; P05803; -.
DR ABCD; P05803; 1 sequenced antibody.
DR EvolutionaryTrace; P05803; -.
DR PRO; PR:P05803; -.
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..470
FT /note="Neuraminidase"
FT /id="PRO_0000078725"
FT TOPO_DOM 1..14
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT TRANSMEM 15..35
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT TOPO_DOM 36..470
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..89
FT /note="Hypervariable stalk region"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 92..470
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 152
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 406
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 119
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 153
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 278..279
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 294
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 295
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT BINDING 299
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT BINDING 326
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT BINDING 348
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT BINDING 372
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 52
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 66
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7517697, ECO:0000269|PubMed:7994573"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) (high mannose) asparagine; by
FT host"
FT /evidence="ECO:0000269|PubMed:7517697"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 93..419
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT DISULFID 125..130
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT DISULFID 177..195
FT /evidence="ECO:0000269|PubMed:7994573"
FT DISULFID 185..232
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT DISULFID 234..239
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT DISULFID 280..293
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT DISULFID 282..291
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT DISULFID 320..338
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT DISULFID 423..449
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071,
FT ECO:0000269|PubMed:7994573"
FT STRAND 96..104
FT /evidence="ECO:0007829|PDB:1NMB"
FT HELIX 106..110
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 138..143
FT /evidence="ECO:0007829|PDB:1NMB"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:1NMB"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:1NMB"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 174..186
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 204..218
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:1NCD"
FT STRAND 238..246
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 252..260
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 263..269
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 288..292
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 303..308
FT /evidence="ECO:0007829|PDB:1NMB"
FT TURN 309..312
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 354..357
FT /evidence="ECO:0007829|PDB:1NMA"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:2B8H"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 369..379
FT /evidence="ECO:0007829|PDB:1NMB"
FT TURN 381..385
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 392..403
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 407..410
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 415..420
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 423..431
FT /evidence="ECO:0007829|PDB:1NMB"
FT TURN 432..434
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 437..439
FT /evidence="ECO:0007829|PDB:1NMB"
FT STRAND 441..453
FT /evidence="ECO:0007829|PDB:1NMB"
FT HELIX 466..469
FT /evidence="ECO:0007829|PDB:1NMB"
SQ SEQUENCE 470 AA; 52394 MW; F2054DD47BBAB996 CRC64;
MNPNQKILCT SATALVIGTI AVLIGIVNLG LNIGLHLKPS CNCSRSQPEA TNASQTIINN
YYNETNITQI SNTNIQVEER ASREFNNLTK GLCTINSWHI YGKDNAVRIG EDSDVLVTRE
PYVSCDPDEC RFYALSQGTT IRGKHSNGTI HDRSQYRDLI SWPLSSPPTV YNSRVECIGW
SSTSCHDGRA RMSICISGPN NNASAVIWYN RRPVTEINTW ARNILRTQES ECVCQNGVCP
VVFTDGSATG PAETRIYYFK EGKILKWEPL TGTAKHIEEC SCYGEQAGVT CTCRDNWQGS
NRPVIQIDPV AMTHTSQYIC SPVLTDNPRP NDPTVGKCND PYPGNNNNGV KGFSYLDGGN
TWLGRTISIA SRSGYEMLKV PNALTDDRSK PTQGQTIVLN TDWSGYSGSF MDYWAEGECY
RACFYVELIR GRPKEDKVWW TSNSIVSMCS STEFLGQWNW PDGAKIEYFL
