AC   MF_04071;
DC   Protein; auto
TR   HAMAP; MF_04071; -; 1; level=0
XX
Names: INFV_NRAM
XX
ID   NRAM
DE   RecName: Full=Neuraminidase;
DE            EC=3.2.1.18;
GN   Name=NA;
XX
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 moities 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;
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.
CC   -!- SUBCELLULAR LOCATION: Virion membrane. Host apical cell membrane;
CC       Single-pass type II membrane protein. Note=Preferentially accumulates
CC       at 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.
CC   -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis.
CC       Possess 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   -!- PTM: N-glycosylated.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family.
XX
DR   PROSITE; PS00001; ASN_GLYCOSYLATION; 0-unlimited; trigger=yes
DR   Pfam; PF00064; Neur; 1; trigger=no
DR   General; Transmembrane; -; 1; trigger=yes
DR   ADD_TOPO_DOMAIN; Intravirion; -; 1; trigger=yes
DR   ADD_TOPO_DOMAIN; Virion_surface; -; 1; trigger=yes
XX
KW   Calcium
KW   Disulfide bond
KW   Glycoprotein
KW   Glycosidase
KW   Host cell membrane
KW   Host membrane
KW   Hydrolase
KW   Membrane
KW   Metal-binding
KW   Signal-anchor
KW   Transmembrane
KW   Transmembrane helix
KW   Virion
XX
GO   GO:0020002; C:host cell plasma membrane
GO   GO:0016020; C:membrane
GO   GO:0055036; C:virion membrane
GO   GO:0052794; F:exo-alpha-(2->3)-sialidase activity
GO   GO:0052795; F:exo-alpha-(2->6)-sialidase activity
GO   GO:0052796; F:exo-alpha-(2->8)-sialidase activity
GO   GO:0046872; F:metal ion binding
GO   GO:0046761; P:viral budding from plasma membrane
XX
FT   From: NRAM_I34A1 (P03468)
FT   REGION          11..33
FT                   /note="Involved in apical transport and lipid raft
FT                   association"
FT   REGION          36..75
FT                   /note="Hypervariable stalk region"
FT   REGION          76..Cter
FT                   /note="Head of neuraminidase"
FT   BINDING         262..263
FT                   /ligand="substrate"
FT   Condition: E-E
FT   ACT_SITE        136
FT                   /note="Proton donor/acceptor"
FT   Condition: D
FT   ACT_SITE        387
FT                   /note="Nucleophile"
FT   Condition: Y
FT   BINDING         279
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT   Condition: D
FT   BINDING         283
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT   Condition: G
FT   BINDING         309
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT   Condition: D
FT   BINDING         329
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT   Condition: N
FT   BINDING         103
FT                   /ligand="substrate"
FT   Condition: R
FT   BINDING         137
FT                   /ligand="substrate"
FT   Condition: R
FT   BINDING         278
FT                   /ligand="substrate"
FT   Condition: R
FT   BINDING         353
FT                   /ligand="substrate"
FT   Condition: R
FT   DISULFID        77..402
FT   Condition: C-x*-C
FT   DISULFID        109..114
FT   Condition: C-x*-C
FT   DISULFID        169..216
FT   Condition: C-x*-C
FT   DISULFID        218..223
FT   Condition: C-x*-C
FT   DISULFID        264..277
FT   Condition: C-x*-C
FT   DISULFID        266..275
FT   Condition: C-x*-C
FT   DISULFID        303..320
FT   Condition: C-x*-C
FT   DISULFID        406..431
FT   Condition: C-x*-C
FT   From: NRAM_INBBE (P27907)
case <OC:Betainfluenzavirus>
FT   DISULFID        86..419
FT   Condition: C-x*-C
end case
XX
Size: 447-471;
Related: None;
Template: P03468; P27907;
Scope:
 Viruses; Orthomyxoviridae
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
XX
# Revision 1.10 2022/11/19
//