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P05803 (NRAM_I84A1) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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/Whale/Maine/1/1984 H13N9)
Taxonomic identifier11484 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]

Protein attributes

Sequence length470 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. 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.

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_0000078725

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
Metal binding2991Calcium; via carbonyl oxygen
Metal binding3261Calcium
Metal binding3481Calcium; via carbonyl oxygen
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
Glycosylation1471N-linked (GlcNAc...); by host
Glycosylation2021N-linked (GlcNAc...) (high mannose); by host
Disulfide bond93 ↔ 419
Disulfide bond125 ↔ 130
Disulfide bond177 ↔ 195
Disulfide bond185 ↔ 232
Disulfide bond234 ↔ 239
Disulfide bond280 ↔ 293
Disulfide bond282 ↔ 291
Disulfide bond320 ↔ 338
Disulfide bond423 ↔ 449

Secondary structure

......................................................................... 470
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05803 [UniParc].

Last modified November 1, 1988. Version 1.
Checksum: F2054DD47BBAB996

FASTA47052,394
        10         20         30         40         50         60 
MNPNQKILCT SATALVIGTI AVLIGIVNLG LNIGLHLKPS CNCSRSQPEA TNASQTIINN 

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

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

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

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

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

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

       430        440        450        460        470 
RACFYVELIR GRPKEDKVWW TSNSIVSMCS STEFLGQWNW PDGAKIEYFL 

« Hide

References

[1]"Distribution of sequence differences in influenza N9 neuraminidase of tern and whale viruses and crystallization of the whale neuraminidase complexed with antibodies."
Air G.M., Webster R.G., Colman P.M., Laver W.G.
Virology 160:346-354(1987) [PubMed] [Europe PMC] [Abstract]
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.
[5]"The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody."
Malby R.L., Tulip W.R., Harley V.R., McKimm-Breschkin J.L., Laver W.G., Webster R.G., Colman P.M.
Structure 2:733-746(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH THE NC10 ANTIBODY.
[6]"N9 neuraminidase complexes with antibodies NC41 and NC10: empirical free energy calculations capture specificity trends observed with mutant binding data."
Tulip W.R., Harley V.R., Webster R.G., Novotny J.
Biochemistry 33:7986-7997(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 83-470 IN COMPLEX WITH ANTIBODIES NC41 AND NC10.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M17812 Genomic RNA. Translation: AAA43575.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NCDX-ray2.90N83-470[»]
1NMAX-ray3.00N83-470[»]
1NMBX-ray2.20N1-470[»]
2B8HX-ray2.20A/B/C/D83-470[»]
ProteinModelPortalP05803.
SMRP05803. Positions 83-470.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-1511103.

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

EvolutionaryTraceP05803.
PROP05803.

Entry information

Entry nameNRAM_I84A1
AccessionPrimary (citable) accession number: P05803
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: February 19, 2014
This is version 110 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