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P06820 (NRAM_I67A0) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 111. 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/Tokyo/3/1967 H2N2)
Taxonomic identifier380960 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length469 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.

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 – 469469Neuraminidase
PRO_0000078720

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 3529Helical; Signal-anchor for type II membrane protein; Potential
Topological domain36 – 469434Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 9055Hypervariable stalk region
Region91 – 469379Head of neuraminidase
Compositional bias179 – 1824Poly-Ser

Sites

Active site1511 Potential
Active site2761 Potential
Active site4061 Potential
Metal binding2931Calcium; via carbonyl oxygen By similarity
Metal binding2971Calcium; via carbonyl oxygen By similarity
Metal binding3241Calcium By similarity
Binding site1181Substrate Potential
Binding site2921Substrate Potential
Binding site3711Substrate Potential

Amino acid modifications

Glycosylation611N-linked (GlcNAc...); by host Potential
Glycosylation691N-linked (GlcNAc...); by host Potential
Glycosylation701N-linked (GlcNAc...); by host Potential
Glycosylation861N-linked (GlcNAc...); by host
Glycosylation1461N-linked (GlcNAc...); by host
Glycosylation2001N-linked (GlcNAc...); by host
Glycosylation2341N-linked (GlcNAc...); by host
Disulfide bond92 ↔ 417
Disulfide bond124 ↔ 129
Disulfide bond175 ↔ 193
Disulfide bond183 ↔ 230
Disulfide bond232 ↔ 237
Disulfide bond278 ↔ 291
Disulfide bond280 ↔ 289
Disulfide bond318 ↔ 337
Disulfide bond421 ↔ 447

Experimental info

Sequence conflict411E → D in AAO46245. Ref.3

Secondary structure

................................................................................. 469
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06820 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: DF9F74BFFA3FEBC9

FASTA46952,131
        10         20         30         40         50         60 
MNPNQKIITI GSVSLTIATV CFLMQIAILV TTVTLHFKQH ECDSPASNQV MPCEPIIIER 

        70         80         90        100        110        120 
NITEIVYLNN TTIEKEICPK VVEYRNWSKP QCQITGFAPF SKDNSIRLSA GGDIWVTREP 

       130        140        150        160        170        180 
YVSCDPVKCY QFALGQGTTL DNKHSNDTVH DRIPHRTLLM NELGVPFHLG TRQVCIAWSS 

       190        200        210        220        230        240 
SSCHDGKAWL HVCITGDDKN ATASFIYDGR LVDSIGSWSQ NILRTQESEC VCINGTCTVV 

       250        260        270        280        290        300 
MTDGSASGRA DTRILFIEEG KIVHISPLAG SAQHVEECSC YPRYPGVRCI CRDNWKGSNR 

       310        320        330        340        350        360 
PVVDINMEDY SIDSSYVCSG LVGDTPRNDD RSSNSNCRNP NNERGTQGVK GWAFDNGNDL 

       370        380        390        400        410        420 
WMGRTISKDL RSGYETFKVI GGWSTPNSKS QINRQVIVDS DNRSGYSGIF SVEGKSCINR 

       430        440        450        460 
CFYVELIRGR KQETRVWWTS NSIVVFCGTS GTYGTGSWPD GANINFMPI 

« Hide

References

[1]"Sequence of the neuraminidase gene of influenza virus A/Tokyo/3/67 and previously uncharacterized monoclonal variants."
Lentz M.R., Air G.M., Laver W.G., Webster R.G.
Virology 135:257-265(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]Air G.M.
Submitted (JUL-1996) to UniProtKB
Cited for: SEQUENCE REVISION TO 420.
[3]"Genetic analysis of human H2N2 and early H3N2 influenza viruses, 1957-1972: evidence for genetic divergence and multiple reassortment events."
Lindstrom S.E., Cox N.J., Klimov A.
Virology 328:101-119(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[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.
[7]"Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2-A resolution."
Varghese J.N., Colman P.M.
J. Mol. Biol. 221:473-486(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 82-469.
[8]"A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies."
White C.L., Janakiraman M.N., Laver W.G., Philippon C., Vasella A., Air G.M., Luo M.
J. Mol. Biol. 245:623-634(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 82-469.
[9]"Structures of aromatic inhibitors of influenza virus neuraminidase."
Jedrzejas M.J., Singh S., Brouillette W.J., Laver W.G., Air G.M., Luo M.
Biochemistry 34:3144-3151(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 82-469.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K01393 Genomic RNA. Translation: AAB05621.1.
AY209929 Genomic RNA. Translation: AAO46245.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1INGX-ray2.40A/B82-469[»]
1INHX-ray2.40A/B82-469[»]
1INWX-ray2.40A82-469[»]
1INXX-ray2.40A82-469[»]
1IVCX-ray2.40A/B82-469[»]
1IVDX-ray1.90A/B82-469[»]
1IVEX-ray2.40A/B82-469[»]
1IVFX-ray2.40A/B82-469[»]
1IVGX-ray1.90A/B82-469[»]
1NN2X-ray2.20A82-469[»]
2BATX-ray2.00A82-469[»]
ProteinModelPortalP06820.
SMRP06820. Positions 82-469.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP06820.

Protein family/group databases

CAZyGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKP06820.

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

EvolutionaryTraceP06820.
PROP06820.

Entry information

Entry nameNRAM_I67A0
AccessionPrimary (citable) accession number: P06820
Secondary accession number(s): Q6XUB0
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: October 1, 1996
Last modified: February 19, 2014
This is version 111 of the entry and version 2 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