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P03478 (NRAM_I72A5) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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 A virus (strain A/Shearwater/Australia/1972 H6N5)
Taxonomic identifier383604 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]

Protein attributes

Sequence length468 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 – 468468Neuraminidase
PRO_0000078716

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 3529Helical; Signal-anchor for type II membrane protein; Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 8247Hypervariable stalk region
Region83 – 468386Head of neuraminidase
Compositional bias437 – 4404Poly-Ser

Sites

Active site1431 Potential
Active site2691 Potential
Active site3991 Potential
Metal binding2861Calcium; via carbonyl oxygen By similarity
Metal binding2901Calcium; via carbonyl oxygen By similarity
Metal binding3161Calcium By similarity
Binding site1101Substrate Potential
Binding site2851Substrate Potential
Binding site3651Substrate Potential

Amino acid modifications

Glycosylation461N-linked (GlcNAc...); by host Potential
Glycosylation521N-linked (GlcNAc...); by host Potential
Glycosylation651N-linked (GlcNAc...); by host Potential
Glycosylation781N-linked (GlcNAc...); by host Potential
Glycosylation1381N-linked (GlcNAc...); by host Potential
Glycosylation3951N-linked (GlcNAc...); by host Potential
Disulfide bond84 ↔ 414 By similarity
Disulfide bond116 ↔ 121 By similarity
Disulfide bond176 ↔ 223 By similarity
Disulfide bond225 ↔ 230 By similarity
Disulfide bond271 ↔ 284 By similarity
Disulfide bond273 ↔ 282 By similarity
Disulfide bond310 ↔ 329 By similarity
Disulfide bond418 ↔ 444 By similarity

Experimental info

Sequence conflict261V → G in CAA24278. Ref.3
Sequence conflict31 – 333LGI → WGT in CAA24278. Ref.3
Sequence conflict501V → A in CAA24278. Ref.3
Sequence conflict55 – 595VRVET → ARAEK in CAA24278. Ref.3
Sequence conflict69 – 702YL → HS in CAA24278. Ref.3
Sequence conflict841C → R in CAA24278. Ref.3
Sequence conflict94 – 10714KDNGI…RGHIF → NGHGTRTGQEGTHS in CAA24278. Ref.3
Sequence conflict1151S → A in BAF36387. Ref.2
Sequence conflict3351R → G in BAF36387. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P03478 [UniParc].

Last modified February 1, 1991. Version 2.
Checksum: 58A235445B2D3F1F

FASTA46851,590
        10         20         30         40         50         60 
MNPNQKIITI GSASLGLVIF NILLHVASIT LGIISVTKDN KVHICNTTEV YNETVRVETV 

        70         80         90        100        110        120 
VIPVNNTIYL NHEPEFLNNT EPLCDVSGFA IVSKDNGIRI GSRGHIFVIR EPFVSCGPSE 

       130        140        150        160        170        180 
CRTFFLTQGA LLNDKHSNNT VKDRSPYRAL MSVPLGSSPN AYQAKFESVG WSATACHDGK 

       190        200        210        220        230        240 
KWMAIGVSGA DDDAYAVIHY GGVPTDVIRS WRKQILRTQE SSCVCIKGEC YWVMTDGPAN 

       250        260        270        280        290        300 
NQASYKIFKS QKGMVVDEKE ISFQGGHIEE CSCYPNMGKV ECVCRDNWNG MNRPILIFDE 

       310        320        330        340        350        360 
KLEYEVGYLC AGIPTDTPRV QDSSFTGSCT NAVGRSGTNN YGVKGFGFRQ GNSVWAGRTI 

       370        380        390        400        410        420 
SVSSRSGFEV LLIEDGWIRP SKTISKKVEV LNNKNWSGYS GAFTIPTAMT SKNCIVPCFW 

       430        440        450        460 
LEMIRGKPEE RTSIWTSSSS TVFCGVSSEV PGWSWDDGAI LPFDIDKM 

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References

[1]"Molecular cloning and analysis of the N5 neuraminidase subtype from an avian influenza virus."
Harley V.R., Ward C.W., Hudson P.J.
Virology 169:239-243(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"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 (NOV-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"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 1-107.
[4]"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.
[5]"Neuraminidase inhibitors for influenza."
Moscona A.
N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[6]"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
M24740 Genomic RNA. Translation: AAA43672.1.
AB278601 Genomic RNA. Translation: BAF36387.1.
V01094 Unassigned RNA. Translation: CAA24278.1.
PIRNMIVN5. A00890.

3D structure databases

ProteinModelPortalP03478.
SMRP03478. Positions 76-465.
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...

Other

PROP03478.

Entry information

Entry nameNRAM_I72A5
AccessionPrimary (citable) accession number: P03478
Secondary accession number(s): A0A9J2, Q84104
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1991
Last modified: February 19, 2014
This is version 99 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