HAMAP rule MF_04071
General rule information
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| Accession | MF_04071 |
| Dates | 18-APR-2017 (Created)
19-NOV-2022 (Last updated, Version 10) |
| Name | INFV_NRAM |
| Scope(s) |
Viruses Orthomyxoviridae |
| Template(s) | P03468 (NRAM_I34A1); P27907 (NRAM_INBBE); [ Recover all ] |
| Triggered by |
HAMAP; MF_04071 (Get profile general information and statistics) |
Propagated annotation
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Identifier, protein and gene names
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| Identifier | NRAM |
| Protein name | RecName: Full=Neuraminidase; EC=3.2.1.18; |
| Gene name | Name=NA; |
Comments
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| 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=3.2.1.18; |
| COFACTOR | Name=Ca(2+); Xref=ChEBI: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. |
| 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
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| Calcium |
| Disulfide bond |
| Glycoprotein |
| Glycosidase |
| Host cell membrane |
| Host membrane |
| Hydrolase |
| Membrane |
| Metal-binding |
| Signal-anchor |
| Transmembrane |
| Transmembrane helix |
| Virion |
Gene Ontology
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| 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
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| PROSITE | PS00001; ASN_GLYCOSYLATION; 0-unlimited; |
| Pfam | PF00064; Neur; 1; |
| General | Transmembrane; -; 1; |
| ADD_TOPO_DOMAIN | Intravirion; -; 1; |
| ADD_TOPO_DOMAIN | Virion_surface; -; 1; |
Features
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| 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+)" /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 | |||||||||
| From: NRAM_INBBE (P27907) | ||||||||||||
| Key | From | To | Description | Tag | Condition | FTGroup | ||||||
| case <OC:Betainfluenzavirus> | ||||||||||||
| DISULFID | 86 | 419 | C-x*-C | |||||||||
| end case | ||||||||||||
Additional information
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| Size range | 447-471 amino acids |
| Related rules |
None |
| Fusion | Nter: None Cter: None |