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P03470 (NRAM_I33A0) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein attributes

Sequence length453 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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. Ref.4

Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious. Ref.4

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. Host apical cell membrane; Single-pass type II membrane protein. 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. Ref.3

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.

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 – 453453Neuraminidase
PRO_0000078726

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 3529Helical; Signal-anchor for type II membrane protein; Potential
Topological domain36 – 453418Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association
Region36 – 7439Hypervariable stalk region
Region75 – 453379Head of neuraminidase

Sites

Active site1351 Potential
Active site2611 Potential
Active site3861 Potential
Metal binding2781Calcium; via carbonyl oxygen By similarity
Metal binding2821Calcium; via carbonyl oxygen By similarity
Metal binding3081Calcium By similarity
Metal binding3281Calcium; via carbonyl oxygen By similarity
Binding site1021Substrate Potential
Binding site2771Substrate Potential
Binding site3521Substrate Potential

Amino acid modifications

Glycosylation441N-linked (GlcNAc...); by host Potential
Glycosylation721N-linked (GlcNAc...); by host Potential
Glycosylation1301N-linked (GlcNAc...); by host Potential
Glycosylation2191N-linked (GlcNAc...); by host Potential
Disulfide bond76 ↔ 401 By similarity
Disulfide bond108 ↔ 113 By similarity
Disulfide bond168 ↔ 215 By similarity
Disulfide bond217 ↔ 222 By similarity
Disulfide bond263 ↔ 276 By similarity
Disulfide bond265 ↔ 274 By similarity
Disulfide bond302 ↔ 319 By similarity
Disulfide bond405 ↔ 430 By similarity

Natural variations

Natural variant531I → S in strain: A/WSN/33.
Natural variant56 – 572YN → HK in strain: A/NWS/33.
Natural variant571N → K in strain: A/WSN/33.
Natural variant1301N → R in strain: A/WSN/33.
Natural variant1301N → Y in strain: A/NWS/33.
Natural variant1331V → F in strain: A/WSN/33.
Natural variant1331V → S in strain: A/NWS/33.
Natural variant1841N → D in strain: A/WSN/33.
Natural variant2061K → N in strain: A/WSN/33.
Natural variant2321N → D in strain: A/WSN/33 and A/NWS/33.
Natural variant2971Q → K in strain: A/WSN/33.
Natural variant3161P → T in strain: A/WSN/33 and A/NWS/33.
Natural variant3361R → K in strain: A/WSN/33.
Natural variant3731V → M in strain: A/WSN/33.
Natural variant4141R → L in strain: A/WSN/33.
Natural variant4141R → Q in strain: A/NWS/33.
Natural variant418 – 4192ET → DA in strain: A/WSN/33.
Natural variant4341S → G in strain: A/WSN/33.

Experimental info

Sequence conflict1721M → V in AAA43397. Ref.1
Sequence conflict380 – 3823MTD → ITN in AAA43397. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P03470 [UniParc].

Last modified December 20, 2005. Version 2.
Checksum: 76E63E3A97D1EFEC

FASTA45349,687
        10         20         30         40         50         60 
MNPNQKIITI GSICMVVGII SLILQIGNII SIWISHSIQT GNQNHTGICN QGIITYNVVA 

        70         80         90        100        110        120 
GQDSTSVILT GNSSLCPIRG WAIHSKDNGI RIGSKGDVFV IREPFISCSH LECRTFFLTQ 

       130        140        150        160        170        180 
GALLNDKHSN GTVKDRSPYR ALMSCPVGEA PSPYNSRFES VAWSASACHD GMGWLTIGIS 

       190        200        210        220        230        240 
GPDNGAVAVL KYNGIITETI KSWRKKILRT QESECTCVNG SCFTIMTDGP SNGLASYKIF 

       250        260        270        280        290        300 
KIEKGKVTKS IELNAPNSHY EECSCYPDTG KVMCVCRDNW HGSNRPWVSF DQNLDYQIGY 

       310        320        330        340        350        360 
ICSGVFGDNP RPKDGPGSCG PVSADGANGV KGFSYRYGNG VWIGRTKSDS SRHGFEMIWD 

       370        380        390        400        410        420 
PNGWTETDSR FSVRQDVVAM TDRSGYSGSF VQHPELTGLD CMRPCFWVEL IRGRPEEETI 

       430        440        450 
WTSGSIISFC GVNSDTVDWS WPDGAELPFT IDK 

« Hide

References

[1]"Complete nucleotide sequence of the neuraminidase gene of human influenza virus A/WSN/33."
Hiti A.L., Nayak D.P.
J. Virol. 41:730-734(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: A/WSN/33.
[2]"Changes in the neuraminidase of neurovirulent influenza virus strains."
Ward A.C.
Virus Genes 10:253-260(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: A/NWS/33, A/WS/33 and A/WSN/33.
[3]"Analysis of the transmembrane domain of influenza virus neuraminidase, a type II transmembrane glycoprotein, for apical sorting and raft association."
Barman S., Nayak D.P.
J. Virol. 74:6538-6545(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[4]"Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication."
Suzuki T., Takahashi T., Guo C.T., Hidari K.I., Miyamoto D., Goto H., Kawaoka Y., Suzuki Y.
J. Virol. 79:11705-11715(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
Strain: A/WSN/33.
[5]"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.
[6]"Neuraminidase inhibitors for influenza."
Moscona A.
N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[7]"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
J02177 Genomic RNA. Translation: AAA43397.1. Sequence problems.
L25815 mRNA. Translation: AAA91326.1.
L25816 mRNA. Translation: AAA91327.1.
L25817 mRNA. Translation: AAA91328.1.

3D structure databases

ProteinModelPortalP03470.
SMRP03470. Positions 67-451.
ModBaseSearch...
MobiDBSearch...

Chemistry

ChEMBLCHEMBL1287610.

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_I33A0
AccessionPrimary (citable) accession number: P03470
Secondary accession number(s): Q67215, Q67216, Q67217
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 20, 2005
Last modified: February 19, 2014
This is version 103 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