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HAMAP rule MF_04071

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General rule information [?]

Accession MF_04071
Dates 18-APR-2017 (Created)
19-NOV-2022 (Last updated, Version 10)
Scope(s) Viruses
Template(s) P03468 (NRAM_I34A1); P27907 (NRAM_INBBE); [ Recover all ]
Triggered by HAMAP; MF_04071 (Get profile general information and statistics)

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier NRAM
Protein name RecName: Full=Neuraminidase;
Gene name Name=NA;

Comments [?]

FUNCTIONCatalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft- association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.
CATALYTIC ACTIVITY Reaction=Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha- (2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.; EC=;
COFACTOR Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
ACTIVITY REGULATIONInhibited by the neuraminidase inhibitors zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs interfere with the release of progeny virus from infected cells and are effective against all influenza strains. Resistance to neuraminidase inhibitors is quite rare.
SUBCELLULAR LOCATIONVirion membrane. Host apical cell membrane; Single-pass type II membrane protein. Note=Preferentially accumulates at the apical plasma membrane in infected polarized epithelial cells, which is the virus assembly site. Uses lipid rafts for cell surface transport and apical sorting. In the virion, forms a mushroom-shaped spike on the surface of the membrane.
DOMAINIntact N-terminus is essential for virion morphogenesis. Possess two apical sorting signals, one in the ectodomain, which is likely to be a glycan, and the other in the transmembrane domain. The transmembrane domain also plays a role in lipid raft association.
SIMILARITYBelongs to the glycosyl hydrolase 34 family.

Keywords [?]

Gene Ontology [?]

GO:0020002; Cellular component:host cell plasma membrane
GO:0016020; Cellular component:membrane
GO:0055036; Cellular component:virion membrane
GO:0052794; Molecular function:exo-alpha-(2->3)-sialidase activity
GO:0052795; Molecular function:exo-alpha-(2->6)-sialidase activity
GO:0052796; Molecular function:exo-alpha-(2->8)-sialidase activity
GO:0046872; Molecular function:metal ion binding
GO:0046761; Biological process:viral budding from plasma membrane

Cross-references [?]

Pfam PF00064; Neur; 1;
General Transmembrane; -; 1;
ADD_TOPO_DOMAIN Intravirion; -; 1;
ADD_TOPO_DOMAIN Virion_surface; -; 1;

Features [?]

From: NRAM_I34A1 (P03468)
Key From To Description Tag Condition FTGroup
REGION 11 33 /note="Involved in apical transport and lipid raft association"
REGION 36 75 /note="Hypervariable stalk region"
REGION 76 Cter /note="Head of neuraminidase"
BINDING 262 263 /ligand="substrate" E-E
ACT_SITE 136 136 /note="Proton donor/acceptor" D
ACT_SITE 387 387 /note="Nucleophile" Y
BINDING 279 279 /ligand="Ca(2+)"
BINDING 283 283 /ligand="Ca(2+)"
BINDING 309 309 /ligand="Ca(2+)"
BINDING 329 329 /ligand="Ca(2+)"
BINDING 103 103 /ligand="substrate" R
BINDING 137 137 /ligand="substrate" R
BINDING 278 278 /ligand="substrate" R
BINDING 353 353 /ligand="substrate" R
DISULFID 77 402 C-x*-C
DISULFID 109 114 C-x*-C
DISULFID 169 216 C-x*-C
DISULFID 218 223 C-x*-C
DISULFID 264 277 C-x*-C
DISULFID 266 275 C-x*-C
DISULFID 303 320 C-x*-C
DISULFID 406 431 C-x*-C
From: NRAM_INBBE (P27907)
Key From To Description Tag Condition FTGroup
case <OC:Betainfluenzavirus>
DISULFID 86 419 C-x*-C
end case

Additional information [?]

Size range 447-471 amino acids
Related rules None
Fusion Nter: None Cter: None

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