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Q9EA42 (NRAM_I77A4) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 72. 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/Swine/Colorado/1/1977 H3N2) [Complete proteome]
Taxonomic identifier385645 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length469 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 – 469469Neuraminidase
PRO_0000280157

Regions

Topological domain1 – 99Intravirion Potential
Transmembrane10 – 3021Helical; Signal-anchor for type II membrane protein; Potential
Topological domain31 – 469439Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 9055Hypervariable stalk region By similarity
Region91 – 469379Head of neuraminidase By similarity
Compositional bias331 – 3355Poly-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
Glycosylation701N-linked (GlcNAc...); by host Potential
Glycosylation861N-linked (GlcNAc...); by host Potential
Glycosylation1461N-linked (GlcNAc...); by host Potential
Glycosylation2001N-linked (GlcNAc...); by host Potential
Glycosylation2341N-linked (GlcNAc...); by host Potential
Glycosylation3131N-linked (GlcNAc...); by host Potential
Glycosylation4021N-linked (GlcNAc...); by host Potential
Disulfide bond92 ↔ 417 By similarity
Disulfide bond124 ↔ 129 By similarity
Disulfide bond183 ↔ 230 By similarity
Disulfide bond232 ↔ 237 By similarity
Disulfide bond278 ↔ 291 By similarity
Disulfide bond280 ↔ 289 By similarity
Disulfide bond318 ↔ 337 By similarity
Disulfide bond421 ↔ 447 By similarity

Experimental info

Sequence conflict101I → L in AAG01743. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9EA42 [UniParc].

Last modified September 11, 2007. Version 2.
Checksum: 5CFFB7F4E24E04F6

FASTA46952,099
        10         20         30         40         50         60 
MNPNQKIITI GSVSLTIATI CFLMQIAILV TTVTLHFKQY ECDYPANNQA MPCEPIIIER 

        70         80         90        100        110        120 
NITEIVYLTN TTIEKEVCPK LVEYRNWSKP QCKITGFAPF SKDNSIRLSA GGDIWVTREP 

       130        140        150        160        170        180 
YVSCDPGKCY QFALGQGTTL DNKHSNDTIH DRTPHRTLLM NELGVPFHLG TRQVCIAWSS 

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

       250        260        270        280        290        300 
MTDGSASGRA DTKILFIEEG KIVHTSPLSG SAQHVEECSC YPRYPGVRCI CRDNWKGSNR 

       310        320        330        340        350        360 
PVVDINVKDY SINSSYVCSG LVGDTPRNND RSSSSYCQNP NNEKGTHGVK GWAFDDGNDV 

       370        380        390        400        410        420 
WMGRTISEDS RSGYETFKVI GGWSTPNSKL QINRQVIVDS DNRSGYSGIF SVEGKSCINR 

       430        440        450        460 
CFYVELIRGR EQETRVWWTS NSIVVFCGTS GTYGTGSWPD GADINIMPI 

« Hide

References

[1]"Genetic characterization of H3N2 influenza viruses isolated from pigs in North America, 1977-1999: evidence for wholly human and reassortant virus genotypes."
Karasin A.I., Schutten M.M., Cooper L.A., Smith C.B., Subbarao K., Anderson G.A., Carman S., Olsen C.W.
Virus Res. 68:71-85(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"The NIAID influenza genome sequencing project."
Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y. expand/collapse author list , Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"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.
[4]"Neuraminidase inhibitors for influenza."
Moscona A.
N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[5]"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
AF251389 Genomic RNA. Translation: AAG01743.1.
CY009302 Genomic RNA. Translation: ABD61554.1.

3D structure databases

ProteinModelPortalQ9EA42.
SMRQ9EA42. Positions 82-469.
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_I77A4
AccessionPrimary (citable) accession number: Q9EA42
Secondary accession number(s): Q288Z3
Entry history
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: September 11, 2007
Last modified: February 19, 2014
This is version 72 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

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries