NRAM_I72A5
ID NRAM_I72A5 Reviewed; 468 AA.
AC P03478; A0A9J2; Q84104;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 133.
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/Shearwater/Australia/1972 H6N5).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=383604;
OH NCBI_TaxID=8782; Aves.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2922926; DOI=10.1016/0042-6822(89)90063-9;
RA Harley V.R., Ward C.W., Hudson P.J.;
RT "Molecular cloning and analysis of the N5 neuraminidase subtype from an
RT avian influenza virus.";
RL Virology 169:239-243(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Kida H., Sakoda Y.;
RT "Establishment of gene library of all haemagglutinin (HA) and neuraminidase
RT (NA) subtypes for the control of influenza A virus infection.";
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-107.
RX PubMed=6896994; DOI=10.1021/bi00260a015;
RA Blok J., Air G.M.;
RT "Variation in the membrane-insertion and 'stalk' sequences in eight
RT subtypes of influenza type A virus neuraminidase.";
RL Biochemistry 21:4001-4007(1982).
RN [4]
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 [5]
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 [6]
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: 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 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-
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 -!- 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; M24740; AAA43672.1; -; Genomic_RNA.
DR EMBL; AB278601; BAF36387.1; -; Genomic_RNA.
DR EMBL; V01094; CAA24278.1; -; Unassigned_RNA.
DR PIR; A00890; NMIVN5.
DR SMR; P03478; -.
DR CAZy; GH34; Glycoside Hydrolase Family 34.
DR PRO; PR:P03478; -.
DR Proteomes; UP000157292; 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 3: Inferred from homology;
KW Calcium; Disulfide bond; Glycoprotein; Glycosidase; Host cell membrane;
KW Host membrane; Hydrolase; Membrane; Metal-binding; Signal-anchor;
KW Transmembrane; Transmembrane helix; Virion.
FT CHAIN 1..468
FT /note="Neuraminidase"
FT /id="PRO_0000078716"
FT TOPO_DOM 1..15
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT TOPO_DOM 37..468
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..80
FT /note="Hypervariable stalk region"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT REGION 83..468
FT /note="Head of neuraminidase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 143
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT ACT_SITE 399
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 110
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 144
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 269..270
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 285
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 286
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 290
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 316
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT BINDING 365
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 46
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 65
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 84..414
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 116..121
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 176..223
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 225..230
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 271..284
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 273..282
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 310..329
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT DISULFID 418..444
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071"
FT CONFLICT 26
FT /note="V -> G (in Ref. 3; CAA24278)"
FT CONFLICT 31..33
FT /note="LGI -> WGT (in Ref. 3; CAA24278)"
FT CONFLICT 50
FT /note="V -> A (in Ref. 3; CAA24278)"
FT CONFLICT 55..59
FT /note="VRVET -> ARAEK (in Ref. 3; CAA24278)"
FT CONFLICT 69..70
FT /note="YL -> HS (in Ref. 3; CAA24278)"
FT CONFLICT 84
FT /note="C -> R (in Ref. 3; CAA24278)"
FT CONFLICT 94..107
FT /note="KDNGIRIGSRGHIF -> NGHGTRTGQEGTHS (in Ref. 3;
FT CAA24278)"
FT CONFLICT 115
FT /note="S -> A (in Ref. 2; BAF36387)"
FT CONFLICT 335
FT /note="R -> G (in Ref. 2; BAF36387)"
SQ SEQUENCE 468 AA; 51590 MW; 58A235445B2D3F1F CRC64;
MNPNQKIITI GSASLGLVIF NILLHVASIT LGIISVTKDN KVHICNTTEV YNETVRVETV
VIPVNNTIYL NHEPEFLNNT EPLCDVSGFA IVSKDNGIRI GSRGHIFVIR EPFVSCGPSE
CRTFFLTQGA LLNDKHSNNT VKDRSPYRAL MSVPLGSSPN AYQAKFESVG WSATACHDGK
KWMAIGVSGA DDDAYAVIHY GGVPTDVIRS WRKQILRTQE SSCVCIKGEC YWVMTDGPAN
NQASYKIFKS QKGMVVDEKE ISFQGGHIEE CSCYPNMGKV ECVCRDNWNG MNRPILIFDE
KLEYEVGYLC AGIPTDTPRV QDSSFTGSCT NAVGRSGTNN YGVKGFGFRQ GNSVWAGRTI
SVSSRSGFEV LLIEDGWIRP SKTISKKVEV LNNKNWSGYS GAFTIPTAMT SKNCIVPCFW
LEMIRGKPEE RTSIWTSSSS TVFCGVSSEV PGWSWDDGAI LPFDIDKM
