ID   NRAM_I78A0              Reviewed;         102 AA.
AC   P03481;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   23-FEB-2022, entry version 108.
DE   RecName: Full=Neuraminidase;
DE            EC=3.2.1.18;
DE   Flags: Fragment;
GN   Name=NA;
OS   Influenza A virus (strain A/Black duck/Australia/702/1978 H3N8).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=385637;
OH   NCBI_TaxID=8782; Aves.
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.
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}.
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DR   EMBL; V01097; CAA24280.1; -; Unassigned_RNA.
DR   EMBL; K01002; AAA43359.1; -; 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..>102
FT                   /note="Neuraminidase"
FT                   /id="PRO_0000078677"
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..>102
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          37..88
FT                   /note="Hypervariable stalk region"
FT   REGION          89..>102
FT                   /note="Head of neuraminidase"
FT   CARBOHYD        46
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        84
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   NON_TER         102
SQ   SEQUENCE   102 AA;  11626 MW;  22D9F38E8660AD66 CRC64;
     MNPNQKIITI GSVSLGLVCL DILLHIISIT ITVLGLHKNG KQRRCNETVI REDNETVRIE
     KVTQWHNTNV IEYIEKLEGD HFMNNTEPLC HAKGFALFSK DN