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Q0A2I4 (NRAM_I83A5) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 43. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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/Chicken/Pennsylvania/1/1983 H5N2) [Complete proteome]
Taxonomic identifier385586 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]

Protein attributes

Sequence length449 AA.
Sequence statusComplete.
Protein existenceInferred from homology

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 – 449449Neuraminidase
PRO_0000280124

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 2923Helical; Signal-anchor for type II membrane protein; Potential
Topological domain30 – 449420Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 7035Hypervariable stalk region By similarity
Region71 – 449379Head of neuraminidase By similarity
Compositional bias311 – 3155Poly-Ser

Sites

Active site1311 Potential
Active site2561 Potential
Active site3861 Potential
Metal binding2731Calcium; via carbonyl oxygen By similarity
Metal binding2771Calcium; via carbonyl oxygen By similarity
Metal binding3041Calcium By similarity
Binding site981Substrate Potential
Binding site2721Substrate Potential
Binding site3511Substrate Potential

Amino acid modifications

Glycosylation321N-linked (GlcNAc...); by host Potential
Glycosylation481N-linked (GlcNAc...); by host Potential
Glycosylation661N-linked (GlcNAc...); by host Potential
Glycosylation1231N-linked (GlcNAc...); by host Potential
Glycosylation1261N-linked (GlcNAc...); by host Potential
Glycosylation1801N-linked (GlcNAc...); by host Potential
Glycosylation2141N-linked (GlcNAc...); by host Potential
Glycosylation3821N-linked (GlcNAc...); by host Potential
Disulfide bond72 ↔ 397 By similarity
Disulfide bond104 ↔ 109 By similarity
Disulfide bond163 ↔ 210 By similarity
Disulfide bond212 ↔ 217 By similarity
Disulfide bond258 ↔ 271 By similarity
Disulfide bond260 ↔ 269 By similarity
Disulfide bond298 ↔ 317 By similarity
Disulfide bond401 ↔ 427 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q0A2I4 [UniParc].

Last modified October 17, 2006. Version 1.
Checksum: DC716FBFB147ADA1

FASTA44949,693
        10         20         30         40         50         60 
MNPNQKIITI GSVSLTIATV CFLMQIAILA TNVTLHFRQN ERSIPAYNQT TPCKPIIIER 

        70         80         90        100        110        120 
NIKYRNWSKP QCQITGFAPF SKDNSIRLSA GGGIWVTREP YVSCDPSKCY QFALGQGTTL 

       130        140        150        160        170        180 
DNNHSNGTIH DRTPHRTLLM NELGVPFHLG TRQVCIAWSS SSCHDGKAWL HVCVTGDDRN 

       190        200        210        220        230        240 
ATASFIYNGM LVDSIGSWSQ NILRTQESEC VCINGTCTVV MTDGSASGKA DIRILFIREG 

       250        260        270        280        290        300 
KIVHISPLSG SAQHIEECSC YPRYPNVRCV CRDNWKGSNR PVIDINMADY SIDSSYVCSG 

       310        320        330        340        350        360 
LVGDTPRNDD SSSSSNCRDP NNERGNPGVK GWAFDIGDDV WMGRTISKDS RSGYETFRVI 

       370        380        390        400        410        420 
GGWATANSKS QTNRQVIVDN NNWSGYSGIF SVESKSCINR CFYVELIRGR PQETRVWWTS 

       430        440 
NSIVVFCGTS GTYGTGSWPD GANINFMPL 

« Hide

References

[1]"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].
[2]"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.
[3]"Neuraminidase inhibitors for influenza."
Moscona A.
N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[4]"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
CY015075 Genomic RNA. Translation: ABI85098.1.

3D structure databases

ProteinModelPortalQ0A2I4.
SMRQ0A2I4. Positions 62-449.
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...

Entry information

Entry nameNRAM_I83A5
AccessionPrimary (citable) accession number: Q0A2I4
Entry history
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: October 17, 2006
Last modified: February 19, 2014
This is version 43 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

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries