Q6J8E4 (NRAM_I03A0) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 56. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Influenza A virus (strain A/Hong Kong/212/2003 H5N1 genotype Z+)|
|Taxonomic identifier||279794 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A ›|
|Virus host||Aves [TaxID: 8782]|
Felis catus (Cat) (Felis silvestris catus) [TaxID: 9685]
Homo sapiens (Human) [TaxID: 9606]
Panthera pardus (Leopard) (Felis pardus) [TaxID: 9691]
Panthera tigris (Tiger) [TaxID: 9694]
Sus scrofa (Pig) [TaxID: 9823]
|Sequence length||469 AA.|
|Protein existence||Inferred from homology|
General annotation (Comments)
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.
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.
Binds 1 calcium ion By similarity.
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.
Homotetramer By similarity.
Virion membrane By similarity. Host apical cell membrane; Single-pass type II membrane protein By similarity. 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 By similarity.
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 By similarity.
N-glycosylated By similarity.
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.
Belongs to the glycosyl hydrolase 34 family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – ›469||›469||Neuraminidase||PRO_0000310941|
|Topological domain||1 – 12||12||Intravirion Potential|
|Transmembrane||13 – 33||21||Helical; Potential|
|Topological domain||34 – ›469||›436||Virion surface Potential|
|Region||11 – 33||23||Involved in apical transport and lipid raft association By similarity|
|Region||36 – 90||55||Hypervariable stalk region By similarity|
|Region||91 – ›469||›379||Head of neuraminidase By similarity|
|Metal binding||294||1||Calcium; via carbonyl oxygen By similarity|
|Metal binding||298||1||Calcium; via carbonyl oxygen By similarity|
|Metal binding||324||1||Calcium By similarity|
|Binding site||118||1||Substrate Potential|
|Binding site||293||1||Substrate Potential|
|Binding site||368||1||Substrate Potential|
Amino acid modifications
|Glycosylation||50||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||58||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||63||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||68||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||88||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||146||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||235||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||386||1||N-linked (GlcNAc...); by host Potential|
|Disulfide bond||92 ↔ 417||By similarity|
|Disulfide bond||124 ↔ 129||By similarity|
|Disulfide bond||184 ↔ 231||By similarity|
|Disulfide bond||233 ↔ 238||By similarity|
|Disulfide bond||279 ↔ 292||By similarity|
|Disulfide bond||281 ↔ 290||By similarity|
|Disulfide bond||421 ↔ 446||By similarity|
|||"H5N1 influenza: a protean pandemic threat."|
Guan Y., Poon L.L.M., Cheung C.Y., Ellis T.M., Lim W., Lipatov A.S., Chan K.H., Sturm-Ramirez K.M., Cheung C.L., Leung Y.H.C., Yuen K.Y., Webster R.G., Peiris J.S.M.
Proc. Natl. Acad. Sci. U.S.A. 101:8156-8161(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|AY575881 Genomic DNA. Translation: AAT39081.1.|
3D structure databases
|SMR||Q6J8E4. Positions 83-467. |
Protein family/group databases
|CAZy||GH34. Glycoside Hydrolase Family 34. |
Protocols and materials databases
Family and domain databases
|Gene3D||18.104.22.168. 1 hit. |
|InterPro||IPR001860. Glyco_hydro_34. |
|Pfam||PF00064. Neur. 1 hit. |
|SUPFAM||SSF50939. SSF50939. 1 hit. |
|Accession||Primary (citable) accession number: Q6J8E4|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|