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P31510 (NRAM_I85A8) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 88. 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 namesRecommended name:
Neuraminidase

EC=3.2.1.18
Gene names
Name:NA
OrganismInfluenza A virus (strain A/Ruddy Turnstone/New Jersey/60/1985 H4N9)
Taxonomic identifier31662 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]

Protein attributes

Sequence length470 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 – 470470Neuraminidase
PRO_0000078715

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 3529Helical; Signal-anchor for type II membrane protein; Potential
Topological domain36 – 470435Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 8954Hypervariable stalk region
Region90 – 470381Head of neuraminidase
Compositional bias345 – 3484Poly-Asn

Sites

Active site1521 Potential
Active site2781 Potential
Active site4061 Potential
Metal binding2951Calcium; via carbonyl oxygen By similarity
Metal binding2991Calcium; via carbonyl oxygen By similarity
Metal binding3261Calcium By similarity
Metal binding3481Calcium; via carbonyl oxygen By similarity
Binding site1191Substrate Potential
Binding site2941Substrate Potential
Binding site3721Substrate Potential

Amino acid modifications

Glycosylation421N-linked (GlcNAc...); by host Potential
Glycosylation521N-linked (GlcNAc...); by host Potential
Glycosylation631N-linked (GlcNAc...); by host Potential
Glycosylation661N-linked (GlcNAc...); by host Potential
Glycosylation871N-linked (GlcNAc...); by host Potential
Glycosylation1471N-linked (GlcNAc...); by host Potential
Glycosylation2021N-linked (GlcNAc...); by host Potential
Disulfide bond93 ↔ 419 By similarity
Disulfide bond125 ↔ 130 By similarity
Disulfide bond177 ↔ 195 By similarity
Disulfide bond185 ↔ 232 By similarity
Disulfide bond234 ↔ 239 By similarity
Disulfide bond280 ↔ 293 By similarity
Disulfide bond282 ↔ 291 By similarity
Disulfide bond320 ↔ 338 By similarity
Disulfide bond423 ↔ 449 By similarity

Sequences

Sequence LengthMass (Da)Tools
P31510 [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: 28C5BECE89DBEA45

FASTA47052,487
        10         20         30         40         50         60 
MNPNQKILFA SATAIVIGTI AVLIGIVNLG LNIGLHLKPS CNCSRSQPEA TNASQTIINN 

        70         80         90        100        110        120 
YYNKTNITQI SNTNIQVEER ASREFNNLTK GLCTINSWHI YGKDNAVRIG EDSDVLVTRE 

       130        140        150        160        170        180 
PYVSCDPDEC RFYALSQGTT IRGKHSNGTI HDRSQYRALI SWPLSSPPTV YNSRVECIGW 

       190        200        210        220        230        240 
SSTSCHDGRA RMSICISGPN NNASAVIWYN RRPVTEINTW ARNILRTQES ECVCHNGVCP 

       250        260        270        280        290        300 
VVFTDGSATG PAETRIYYFK EGKILKWEPL TGTAKHIEEC SCYGEQARVT CTCRDNWQGS 

       310        320        330        340        350        360 
NRPVIQIDPV AMTHTSQYIC SPVLTDNPRP NDPTVGKCND PYPGNNNNGV KGFSYLDGGN 

       370        380        390        400        410        420 
TWLGRTISTA SRSGYEMLKV PNALTDDRSK PTQGQTIVLN TDWSGYSGSF MDYWAEGECY 

       430        440        450        460        470 
RACFYVELIR GRPKEDRVWW TSNSIVSMCS STEFLGQWNW PDGAKIEYFL 

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References

[1]Air G.M., Laver W.G., Webster R.G.
Submitted (AUG-1990) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"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.
[3]"Neuraminidase inhibitors for influenza."
Moscona A.
N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[4]"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
M37511 Genomic RNA. Translation: AAA43426.1.

3D structure databases

ProteinModelPortalP31510.
SMRP31510. Positions 83-470.
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_I85A8
AccessionPrimary (citable) accession number: P31510
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: February 19, 2014
This is version 88 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

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries