A8C8J7 · NRAM_I07A0

Function

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 moieties 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.

Miscellaneous

The influenza A genome consist of 8 RNA segments. Genetic variation of hemagglutinin and/or neuraminidase genes results in the emergence of new influenza strains. The mechanism of variation can be the result of point mutations or the result of genetic reassortment between segments of two different strains.

Catalytic activity

  • 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:3.2.1.18 (UniProtKB | ENZYME | Rhea)

Cofactor

Ca2+ (UniProtKB | Rhea| CHEBI:29108 )

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.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site118substrate
Active site151Proton donor/acceptor
Binding site152substrate
Binding site277-278substrate
Binding site293substrate
Binding site294Ca2+ (UniProtKB | ChEBI)
Binding site298Ca2+ (UniProtKB | ChEBI)
Binding site324Ca2+ (UniProtKB | ChEBI)
Binding site368substrate
Active site402Nucleophile

GO annotations

AspectTerm
Cellular Componenthost cell plasma membrane
Cellular Componentmembrane
Cellular Componentvirion membrane
Molecular Functionexo-alpha-(2->3)-sialidase activity
Molecular Functionexo-alpha-(2->6)-sialidase activity
Molecular Functionexo-alpha-(2->8)-sialidase activity
Molecular Functionmetal ion binding
Biological Processcarbohydrate metabolic process
Biological Processviral budding from plasma membrane

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Neuraminidase
  • EC number

Gene names

    • Name
      NA

Organism names

Accessions

  • Primary accession
    A8C8J7

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.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-6Intravirion
Transmembrane7-27Helical
Topological domain28-470Virion surface

Keywords

PTM/Processing

Features

Showing features for chain, glycosylation, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00003729631-470Neuraminidase
Glycosylation44N-linked (GlcNAc...) asparagine; by host
Glycosylation58N-linked (GlcNAc...) asparagine; by host
Glycosylation63N-linked (GlcNAc...) asparagine; by host
Glycosylation70N-linked (GlcNAc...) asparagine; by host
Glycosylation88N-linked (GlcNAc...) asparagine; by host
Disulfide bond92↔417
Disulfide bond124↔129
Glycosylation146N-linked (GlcNAc...) asparagine; by host
Disulfide bond184↔231
Disulfide bond233↔238
Glycosylation235N-linked (GlcNAc...) asparagine; by host
Disulfide bond279↔292
Disulfide bond281↔290
Disulfide bond318↔335
Disulfide bond421↔447
Glycosylation434N-linked (GlcNAc...) asparagine; by host
Glycosylation455N-linked (GlcNAc...) asparagine; by host

Post-translational modification

N-glycosylated.

Keywords

PTM databases

Interaction

Subunit

Homotetramer.

Structure

3D structure databases

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region11-33Involved in apical transport and lipid raft association
Region36-90Hypervariable stalk region
Region91-470Head of neuraminidase

Domain

Intact N-terminus is essential for virion morphogenesis. Possesses 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.

Sequence similarities

Belongs to the glycosyl hydrolase 34 family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    470
  • Mass (Da)
    51,658
  • Last updated
    2007-11-13 v1
  • Checksum
    9044ACD3A701081A
MNPNQKIITIGSISIAIGIISLMLQIGNIISMWASHSIQTGSQNHTGICNQRIITYENSTWVNHTYVNINNTNVVTGKDKTSVTLAGNSSLCSISGWAIYTKDNSIRIGSKGDVFVIREPFISCSHLECRTFFLTQGALLNDKHSNGTVKDRSPYRALMSCPLGEAPSPYNSKFESVAWSASACHDGMGWLTIGISGPDNGAVAVLKYNGIITETIKSWKKRILRTQESECVCVNGSCFTIMTDGPSDGAASYKIFKIEKGKVTKSIELNAPNFHYEECSCYPDTGTVMCVCRDNWHGSNRPWVSFNQNLDYQIGYICSGVFGDNPRPKDGKGSCNPVTVDGADGVKGFSYKYGNGVWIGRTKSNKLRKGFEMIWDPNGWTDTDNDFSVKQDVVAITDWSGYSGSFVQHPELTGLDCIRPCFWVELVRGLPRENATIWTSGSSISFCGVDSDTANWSWPDGAELPFTIDK

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
CY026213
EMBL· GenBank· DDBJ
ABV45929.1
EMBL· GenBank· DDBJ
Viral cRNA

Similar Proteins

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