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P03476 (NRAM_I71A2) 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/Turkey/Oregon/1971 H7N3)
Taxonomic identifier385636 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]

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_0000078719

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 2923Helical; Signal-anchor for type II membrane protein; Potential
Topological domain30 – 469440Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region39 – 9052Hypervariable stalk region By similarity
Region91 – 469379Head of neuraminidase By similarity

Sites

Active site1511 Potential
Active site2781 Potential
Active site4051 Potential
Metal binding2941Calcium; via carbonyl oxygen By similarity
Metal binding2981Calcium; via carbonyl oxygen By similarity
Metal binding3241Calcium By similarity
Binding site1181Substrate Potential
Binding site2931Substrate Potential
Binding site3701Substrate Potential

Amino acid modifications

Glycosylation571N-linked (GlcNAc...); by host Potential
Glycosylation661N-linked (GlcNAc...); by host Potential
Glycosylation721N-linked (GlcNAc...); by host Potential
Glycosylation1461N-linked (GlcNAc...); by host Potential
Glycosylation3081N-linked (GlcNAc...); by host Potential
Disulfide bond92 ↔ 416 By similarity
Disulfide bond124 ↔ 129 By similarity
Disulfide bond184 ↔ 231 By similarity
Disulfide bond233 ↔ 238 By similarity
Disulfide bond280 ↔ 292 By similarity
Disulfide bond282 ↔ 290 By similarity
Disulfide bond318 ↔ 336 By similarity
Disulfide bond420 ↔ 447 By similarity

Experimental info

Sequence conflict941F → S in CAA24276. Ref.2
Sequence conflict941F → S in AAA43361. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P03476 [UniParc].

Last modified March 20, 2007. Version 2.
Checksum: 1758078B2ABE0F65

FASTA46951,790
        10         20         30         40         50         60 
MNPNQKIITI GVVNTTLSTI ALLIGVGNLV FNTVIHEKIG NHQTVIHPTI TTPAVPNCSD 

        70         80         90        100        110        120 
TIITYNNTVI NNITTTIITE AERLFKPPLP LCPFRGFFPF HKDNAIRLGE NKDVIVTREP 

       130        140        150        160        170        180 
YVSCDNDNCW SFALAQGALL GTKHSNGTIK DRTPYRSLIR FPIGTAPVLG NYKEICIAWS 

       190        200        210        220        230        240 
SSSCFDGKEW MHVCMTGNDN DASAQIIYAG RMTDSIKSWR KDILRTQESE CQCIGGTCVV 

       250        260        270        280        290        300 
AVTDGPAANS ADHRVYWIRE GRIVKYENVP KTKIQHLEEC SCYVDIDVYC ICRDNWKGSN 

       310        320        330        340        350        360 
RPWMRINNET ILETGYVCSK FHSDTPRPAD PSTVSCDSPS NINGGPGVKG FGFKAGNDVW 

       370        380        390        400        410        420 
LGRTVSTSGR SGFEIIKVTD GWINSPNHAK SVTQTLVSNN DWSGYSGSFI VKTKGCFQPC 

       430        440        450        460 
FYVELIRGRP NKNDDVSWTS NSIVTFCGLD NEPGSGNWPD GSNIGFMPK 

« Hide

References

[1]"Establishment of gene library of all haemagglutinin (HA) and neuraminidase (NA) subtypes for the control of influenza A virus infection."
Kida H., Sakoda Y.
Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Variation in the membrane-insertion and 'stalk' sequences in eight subtypes of influenza type A virus neuraminidase."
Blok J., Air G.M.
Biochemistry 21:4001-4007(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-94.
[3]"Sequence variation at the 3' end of the neuraminidase gene from 39 influenza type A viruses."
Blok J., Air G.M.
Virology 121:211-229(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-94.
[4]"Amelioration of influenza virus pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene."
Cauthen A.N., Swayne D.E., Sekellick M.J., Marcus P.I., Suarez D.L.
J. Virol. 81:1838-1847(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[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
AB276110 Genomic RNA. Translation: BAF34372.1.
V01092 Genomic RNA. Translation: CAA24276.1.
K01011 Genomic RNA. Translation: AAA43361.1.
DQ870890 Genomic RNA. Translation: ABH04381.1.
DQ870896 Genomic RNA. Translation: ABH04387.1.

3D structure databases

ProteinModelPortalP03476.
SMRP03476. Positions 88-469.
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_I71A2
AccessionPrimary (citable) accession number: P03476
Secondary accession number(s): Q05JI0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 20, 2007
Last modified: February 19, 2014
This is version 88 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