NRAM_I76A1
ID NRAM_I76A1 Reviewed; 103 AA.
AC P03479; Q84031;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 23-FEB-2022, entry version 102.
DE RecName: Full=Neuraminidase;
DE EC=3.2.1.18;
DE Flags: Fragment;
GN Name=NA;
OS Influenza A virus (strain A/Duck/Alberta/28/1976 H4N6).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=385638;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6927853; DOI=10.1016/0042-6822(82)90162-3;
RA Blok J., Air G.M.;
RT "Sequence variation at the 3' end of the neuraminidase gene from 39
RT influenza type A viruses.";
RL Virology 121:211-229(1982).
RN [3]
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 [4]
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 [5]
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.
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;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250};
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.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000250}. Host apical cell
CC membrane {ECO:0000250}; Single-pass type II membrane protein
CC {ECO:0000250}. Note=Preferentially accumulates at the apical plasma
CC membrane in infected polarized epithelial cells, which is the virus
CC assembly site. Uses lipid rafts for cell surface transport and apical
CC sorting. In the virion, forms a mushroom-shaped spike on the surface of
CC the membrane (By similarity). {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
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. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; V01095; CAA24279.1; -; Genomic_RNA.
DR EMBL; K01009; AAA43358.1; -; Genomic_RNA.
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-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IEA:UniProtKB-EC.
DR GO; GO:0052795; F:exo-alpha-(2->6)-sialidase activity; IEA:UniProtKB-EC.
DR GO; GO:0052796; F:exo-alpha-(2->8)-sialidase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008152; P:metabolic process; IEA:UniProtKB-KW.
PE 3: Inferred from homology;
KW Calcium; Glycoprotein; Glycosidase; Host cell membrane; Host membrane;
KW Hydrolase; Membrane; Metal-binding; Signal-anchor; Transmembrane;
KW Transmembrane helix; Virion.
FT CHAIN 1..>103
FT /note="Neuraminidase"
FT /id="PRO_0000078682"
FT TOPO_DOM 1..6
FT /note="Intravirion"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..35
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..>103
FT /note="Virion surface"
FT /evidence="ECO:0000255"
FT REGION 11..33
FT /note="Involved in apical transport and lipid raft
FT association"
FT /evidence="ECO:0000250"
FT REGION 36..90
FT /note="Hypervariable stalk region"
FT REGION 91..>103
FT /note="Head of neuraminidase"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CONFLICT 22
FT /note="Q -> L (in Ref. 2; AAA43358)"
FT /evidence="ECO:0000305"
FT NON_TER 103
SQ SEQUENCE 103 AA; 11307 MW; DFB26FB23AD6A5ED CRC64;
MNPNQKIICI SATGMTLSVV SQLIGLANLG LNIGLHFKVG ETPEIGTPSV NETNSTTTII
NYNTQNNFTN VTNIVLIKEE DEMFTNLSKP LCEVNSWHIL SRT
