Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P03474 (NRAM_INBLE) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 105. 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 B virus (strain B/Lee/1940) [Reference proteome]
Taxonomic identifier107412 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus B
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length466 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 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 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. 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 466466Neuraminidase
PRO_0000078732

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 3529Helical; Signal-anchor for type II membrane protein; Potential
Topological domain36 – 466431Virion surface 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...); by host Potential
Glycosylation641N-linked (GlcNAc...); by host Potential
Glycosylation1441N-linked (GlcNAc...); by host Potential
Glycosylation2841N-linked (GlcNAc...); by host 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. Ref.2
Mutagenesis1491D → E: Almost complete loss of enzymatic activity. Ref.2
Mutagenesis1501R → K: Reduced substrate binding. Ref.2
Mutagenesis2231R → K: Reduced substrate binding. Ref.2
Mutagenesis2751E → D: Almost complete loss of enzymatic activity. Ref.2
Mutagenesis3741R → K: 80% loss of catalytic efficiency. Ref.2
Mutagenesis3741R → N: 94% loss of catalytic efficiency. Ref.2
Mutagenesis4091Y → F: Complete loss of enzymatic activity. Ref.2

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P03474 [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

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 78-466.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02095 Genomic RNA. Translation: AAA43749.1.
PIRNMIV4. A00886.
RefSeqNP_056663.1. NC_002209.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP03474.
SMRP03474. Positions 77-466.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP03474.
ChEMBLCHEMBL3377.

Protein family/group databases

CAZyGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID956541.

Enzyme and pathway databases

SABIO-RKP03474.

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

EvolutionaryTraceP03474.

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: February 19, 2014
This is version 105 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