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Reviewed, UniProtKB/Swiss-Prot P03474 (NRAM_INBLE)

Last modified July 22, 2008. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Neuraminidase
    EC=3.2.1.18
Gene names
Name: NA
OrganismInfluenza B virus (strain B/Lee/1940)
Taxonomic identifier107412 [NCBI]
Taxonomic lineageViruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus B
Virus hostHomo sapiens (Human) [TaxID: 9606]

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Protein attributes

Sequence length466 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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 By similarity.

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.

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 membraneBy similarity. Apical cell membrane; Single-pass type II membrane proteinBy similarity. Note= Preferentially accumulates at the apical plasma membrane in infected polarized epithelial cells, which is the virus assembly site. In the virion, forms a mushroom-shaped spike on the surface of the membrane By similarity.

Post-translational modification

N-glycosylated By similarity.

Miscellaneous

The influenza B 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.

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Ontologies

Keywords

   Cellular componentCell membrane
Membrane
Virion
   DomainSignal-anchor
Transmembrane
   Molecular functionGlycosidase
Hydrolase
   PTMGlycoprotein
   Technical term3D-structure

Gene Ontology (GO)

   Cellular componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

virion membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 466466Neuraminidase

Regions

Topological domain1 – 66Cytoplasmic Potential
Transmembrane7 – 3529Signal-anchor for type II membrane protein Potential
Topological domain36 – 466431Extracellular Potential
Region39 – 6931Hypervariable stalk region
Region70 – 466397Head of neuraminidase

Sites

Active site1491 Potential
Active site2751 Potential
Active site4091 Potential
Binding site1161Substrate Potential
Binding site2921Substrate Potential
Binding site3741Substrate Potential

Amino acid modifications

Glycosylation561N-linked (GlcNAc...) Potential
Glycosylation641N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Glycosylation2841N-linked (GlcNAc...) Potential
Disulfide bond87 ↔ 420
Disulfide bond122 ↔ 127
Disulfide bond182 ↔ 229
Disulfide bond231 ↔ 236
Disulfide bond277 ↔ 291
Disulfide bond279 ↔ 289
Disulfide bond318 ↔ 337
Disulfide bond424 ↔ 447

Experimental info

Mutagenesis1171E → G: Reduced substrate binding
Mutagenesis1491D → E: Almost complete loss of enzymatic activity
Mutagenesis1501R → K: Reduced substrate binding
Mutagenesis2231R → K: Reduced substrate binding
Mutagenesis2751E → D: Almost complete loss of enzymatic activity
Mutagenesis3741R → K: 80% loss of catalytic efficiency
Mutagenesis3741R → N: 94% loss of catalytic efficiency
Mutagenesis4091Y → F: Complete loss of enzymatic activity

Secondary structure

1 ...................................................................... 466
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P03474-1 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: E6FF3E634F132263

FASTA46651,442
        10         20         30         40         50         60 
MLPSTVQTLT LLLTSGGVLL SLYVSASLSY LLYSDVLLKF SSTKTTAPTM SLECTNASNA 

        70         80         90        100        110        120 
QTVNHSATKE MTFPPPEPEW TYPRLSCQGS TFQKALLISP HRFGEIKGNS APLIIREPFV 

       130        140        150        160        170        180 
ACGPKECRHF ALTHYAAQPG GYYNGTRKDR NKLRHLVSVK LGKIPTVENS IFHMAAWSGS 

       190        200        210        220        230        240 
ACHDGREWTY IGVDGPDNDA LVKIKYGEAY TDTYHSYAHN ILRTQESACN CIGGDCYLMI 

       250        260        270        280        290        300 
TDGSASGISK CRFLKIREGR IIKEILPTGR VEHTEECTCG FASNKTIECA CRDNSYTAKR 

       310        320        330        340        350        360 
PFVKLNVETD TAEIRLMCTK TYLDTPRPDD GSIAGPCESN GDKWLGGIKG GFVHQRMASK 

       370        380        390        400        410        420 
IGRWYSRTMS KTNRMGMELY VKYDGDPWTD SDALTLSGVM VSIEEPGWYS FGFEIKDKKC 

       430        440        450        460 
DVPCIGIEMV HDGGKDTWHS AATAIYCLMG SGQLLWDTVT GVDMAL

« Hide

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References

[1]"Complete nucleotide sequence of the neuraminidase gene of influenza B virus."
Shaw M.W., Lamb R.A., Erickson B.W., Briedis D.J., Choppin P.W.
Proc. Natl. Acad. Sci. U.S.A. 79:6817-6821(1982) [PubMed: 6294654] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Site-directed mutagenesis of catalytic residues of influenza virus neuraminidase as an aid to drug design."
Ghate A.A., Air G.M.
Eur. J. Biochem. 258:320-331(1998) [PubMed: 9874196] [Abstract]
Cited for: MUTAGENESIS OF GLU-117; ASP-149; ARG-150; ARG-223; GLU-275; ARG-374 AND TYR-409.
[3]"Neuraminidase inhibitors for influenza."
Moscona A.
N. Engl. J. Med. 353:1363-1373(2005) [PubMed: 16192481] [Abstract]
Cited for: REVIEW.
[4]"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: 7880809] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 77-466.
[5]"Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site."
Finley J.B., Atigadda V.R., Duarte F., Zhao J.J., Brouillette W.J., Air G.M., Luo M.
J. Mol. Biol. 293:1107-1119(1999) [PubMed: 10547289] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 77-466.
[6]"A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase."
Lommer B.S., Ali S.M., Bajpai S.N., Brouillette W.J., Air G.M., Luo M.
Acta Crystallogr. D 60:1017-1023(2004) [PubMed: 15159560] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 78-466.

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Cross-references

Sequence databases

J02095 Genomic RNA. Translation: AAA43749.1.
PIRNMIV4. A00886.
RefSeqNP_056663.1.

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1B9SX-ray2.50A77-466[»]
1B9TX-ray2.40A77-466[»]
1B9VX-ray2.35A77-466[»]
1INFX-ray2.40A77-466[»]
1INVX-ray2.40A77-466[»]
1IVBX-ray2.40A77-466[»]
1VCJX-ray2.40A78-466[»]
ModBaseSearch...

Genome annotation databases

GeneID956541.

Family and domain databases

InterProIPR001860. Glyco_hydro_34.
[Graphical view]
PfamPF00064. Neur. 1 hit.
[Graphical view]
ProDomPD000431. Glyco_hydro_34. 1 hit.
[Graphical view] [Entries sharing at least one domain]
BLOCKSSearch...

Other Resources

BindingDBP03474.
LinkHubP03474.
ProtoNetSearch...

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Entry information

Entry nameNRAM_INBLE
AccessionPrimary (citable) accession number: P03474
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 22, 2008