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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)
Viruses; Orthomyxoviridae
Templates P03468 (NRAM_I34A1); P27907 (NRAM_INBBE): [Recover all]

Propagated annotation [?]

Identifier, protein and gene names [?]

Protein name
RecName: Full=Neuraminidase;
Gene name

Comments [?]

Function Catalyzes 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 Ca(2+)
Activity regulation Inhibited 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.
Subunit Homotetramer.
Subcellular location Virion 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.
Domain Intact 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.
Ptm N-glycosylated.
Similarity Belongs 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 [?]

PROSITE PS00001; ASN_GLYCOSYLATION; 0-unlimited; trigger=PRU00498;
Pfam PF00064; Neur; 1;

Computed features [?]

General Transmembrane; -; 1; trigger=yes;
ADD_TOPO_DOMAIN Intravirion; -; 1; trigger=yes;
Virion_surface; -; 1; trigger=yes;

Features [?]

From: NRAM_I34A1 (P03468)
Key     From     To       Description   Tag   Condition   FTGroup
REGION     11     33       Involved in apical transport and lipid raft association        
REGION     36     75       Hypervariable stalk region        
REGION     76     Cter       Head of neuraminidase        
BINDING     262     263       /ligand="substrate     E-E  
ACT_SITE     136     136       Proton donor/acceptor     D  
ACT_SITE     387     387       Nucleophile     Y  
BINDING     279     279       /ligand="Ca(2+)" /ligand_id="ChEBI:CHEBI:29108     D  
BINDING     283     283       /ligand="Ca(2+)" /ligand_id="ChEBI:CHEBI:29108     G  
BINDING     309     309       /ligand="Ca(2+)" /ligand_id="ChEBI:CHEBI:29108     D  
BINDING     329     329       /ligand="Ca(2+)" /ligand_id="ChEBI:CHEBI:29108     N  
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  
case <OC:Betainfluenzavirus>
From: NRAM_INBBE (P27907)
DISULFID     86     419             C-x*-C  
end case

Additional information [?]

Size range 447-471 amino acids
Related rules None
Fusion None