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Q6XV27 (NRAM_I56A2) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 61. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuraminidase

EC=3.2.1.18
Gene names
Name:NA
OrganismInfluenza A virus (strain A/Duck/England/1/1956 H11N6) [Complete proteome]
Taxonomic identifier383550 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]

Protein attributes

Sequence length470 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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

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.

Cofactor

Binds 1 calcium ion By similarity.

Enzyme 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 structure

Homotetramer By similarity.

Subcellular location

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.

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 By similarity.

Post-translational modification

N-glycosylated By similarity.

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.

Sequence similarities

Belongs to the glycosyl hydrolase 34 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 470470Neuraminidase
PRO_0000280127

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 2721Helical; Signal-anchor for type II membrane protein; Potential
Topological domain28 – 470443Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 9055Hypervariable stalk region By similarity
Region91 – 470380Head of neuraminidase By similarity

Sites

Active site1511 Potential
Active site2771 Potential
Active site4061 Potential
Metal binding2941Calcium; via carbonyl oxygen By similarity
Metal binding2981Calcium; via carbonyl oxygen By similarity
Metal binding3251Calcium By similarity
Binding site1181Substrate Potential
Binding site2931Substrate Potential
Binding site3721Substrate Potential

Amino acid modifications

Glycosylation511N-linked (GlcNAc...); by host Potential
Glycosylation541N-linked (GlcNAc...); by host Potential
Glycosylation621N-linked (GlcNAc...); by host Potential
Glycosylation671N-linked (GlcNAc...); by host Potential
Glycosylation701N-linked (GlcNAc...); by host Potential
Glycosylation861N-linked (GlcNAc...); by host Potential
Glycosylation1461N-linked (GlcNAc...); by host Potential
Glycosylation2011N-linked (GlcNAc...); by host Potential
Glycosylation4021N-linked (GlcNAc...); by host Potential
Disulfide bond92 ↔ 419 By similarity
Disulfide bond124 ↔ 129 By similarity
Disulfide bond184 ↔ 231 By similarity
Disulfide bond233 ↔ 238 By similarity
Disulfide bond279 ↔ 292 By similarity
Disulfide bond281 ↔ 290 By similarity
Disulfide bond423 ↔ 449 By similarity

Secondary structure

.................................................................... 470
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q6XV27 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: C3C30CB83D15E0E7

FASTA47051,470
        10         20         30         40         50         60 
MNPNQKIICI SATGMTLSVV SLLVGIANLG LNIGLHYKVG DTPNVNIPNV NGTNSTTTII 

        70         80         90        100        110        120 
NNNTQNNFTN ITNIIQSKGG ERTFLNLTKP LCEVNSWHIL SKDNAIRIGE DAHILVTREP 

       130        140        150        160        170        180 
YLSCDPQGCR MFALSQGTTL RGRHANGTIH DRSPFRALIS WEMGQAPSPY NTRVECIGWS 

       190        200        210        220        230        240 
STSCHDGMSR MSICMSGPNN NASAVVWYGG RPITEIPSWA GNILRTQESE CVCHKGVCPV 

       250        260        270        280        290        300 
VMTDGPANNR AATKIIYFKE GKIQKIEELA GNAQHIEECS CYGAGGVIKC ICRDNWKGAN 

       310        320        330        340        350        360 
RPVITIDPEM MTHTSKYLCS KVLTDTSRPN DPTNGNCDAP ITGGSPDPGV KGFAFLDGEN 

       370        380        390        400        410        420 
SWLGRTISKD SRSGYEMLKV PNAETDIQSG PISNQVIVNN QNWSGYSGAF IDYWANKECF 

       430        440        450        460        470 
NPCFYVELIR GRPKESSVLW TSNSIVALCG SKKRLGSWSW HDGAEIIYFE 

« Hide

References

[1]"Genetic analysis of multiple N3, N4, and N6 influenza A virus neuraminidase genes."
Webby R.J., Humberd J.L., Krauss S.L.
Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Large-scale sequence analysis of avian influenza isolates."
Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., Finkelstein D.B., Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., Webster R.G., Hoffmann E., Krauss S., Zheng J., Zhang Z., Naeve C.W.
Science 311:1576-1580(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Sequence variation at the 3' end of the neuraminidase gene from 39 influenza type A viruses."
Blok J., Air G.M.
Virology 121:211-229(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-71.
[4]"Assembly and budding of influenza virus."
Nayak D.P., Hui E.K., Barman S.
Virus Res. 106:147-165(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[5]"Neuraminidase inhibitors for influenza."
Moscona A.
N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[6]"Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses."
Suzuki Y.
Biol. Pharm. Bull. 28:399-408(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY207549 Genomic DNA. Translation: AAO62063.1.
AB288846 Genomic RNA. Translation: BAF43436.1.
CY014681 Genomic RNA. Translation: ABI84548.1.
K01039 Genomic RNA. Translation: AAA43389.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1V0ZX-ray1.84A/B/C/D82-470[»]
1W1XX-ray2.00A/B/C/D82-470[»]
1W20X-ray2.08A/B/C/D82-470[»]
1W21X-ray2.08A/B/C/D82-470[»]
2CMLX-ray2.15A/B/C/D82-470[»]
ProteinModelPortalQ6XV27.
SMRQ6XV27. Positions 82-470.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

CAZyGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D2.120.10.10. 1 hit.
InterProIPR001860. Glyco_hydro_34.
IPR011040. Sialidases.
[Graphical view]
PfamPF00064. Neur. 1 hit.
[Graphical view]
SUPFAMSSF50939. SSF50939. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ6XV27.
PROQ6XV27.

Entry information

Entry nameNRAM_I56A2
AccessionPrimary (citable) accession number: Q6XV27
Secondary accession number(s): Q83982
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: July 5, 2004
Last modified: February 19, 2014
This is version 61 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries