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P88838 (NRAM_I56A3) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 78. 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/Equine/Prague/1/1956 H7N7)
Taxonomic identifier380337 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Equus caballus (Horse) [TaxID: 9796]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]

Protein attributes

Sequence length469 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 By similarity.

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_0000280138

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 2721Helical; Signal-anchor for type II membrane protein; Potential
Topological domain28 – 469442Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 8752Hypervariable stalk region By similarity
Region88 – 469382Head of neuraminidase By similarity

Sites

Active site1481 Potential
Active site2741 Potential
Active site4031 Potential
Metal binding2911Calcium; via carbonyl oxygen By similarity
Metal binding2951Calcium; via carbonyl oxygen By similarity
Metal binding3221Calcium By similarity
Binding site1151Substrate Potential
Binding site2901Substrate Potential
Binding site3691Substrate Potential

Amino acid modifications

Glycosylation281N-linked (GlcNAc...); by host Potential
Glycosylation321N-linked (GlcNAc...); by host Potential
Glycosylation461N-linked (GlcNAc...); by host Potential
Glycosylation551N-linked (GlcNAc...); by host Potential
Glycosylation561N-linked (GlcNAc...); by host Potential
Glycosylation651N-linked (GlcNAc...); by host Potential
Glycosylation661N-linked (GlcNAc...); by host Potential
Glycosylation851N-linked (GlcNAc...); by host Potential
Glycosylation1431N-linked (GlcNAc...); by host Potential
Glycosylation1981N-linked (GlcNAc...); by host Potential
Glycosylation2321N-linked (GlcNAc...); by host Potential
Glycosylation3561N-linked (GlcNAc...); by host Potential
Glycosylation3991N-linked (GlcNAc...); by host Potential
Disulfide bond89 ↔ 417 By similarity
Disulfide bond121 ↔ 126 By similarity
Disulfide bond181 ↔ 228 By similarity
Disulfide bond230 ↔ 235 By similarity
Disulfide bond276 ↔ 289 By similarity
Disulfide bond278 ↔ 287 By similarity
Disulfide bond421 ↔ 448 By similarity

Experimental info

Sequence conflict851N → K in AAA43411. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P88838 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 38A224BA86D9ADC8

FASTA46951,890
        10         20         30         40         50         60 
MNPNQKLFAS SGIAIALGII NLLIGISNMS LNISLYSKGE NHKSDNLTCT NINQNNTTMV 

        70         80         90        100        110        120 
NTYINNTTII DKNTKMENPG YLLLNKSLCN VEGWVVIAKD NAIRFGESEQ IIVTREPYVS 

       130        140        150        160        170        180 
CDPLSCKMYA LHQGTTIRNK HSNGTTHDRT AFRGLISTPL GNPPTVSNSE FICVGWSSTS 

       190        200        210        220        230        240 
CHDGVSRMTI CVQGNNENAT ATVYYNKRLT TTIKTWAKNI LRTQESECVC HNSTCVVVMT 

       250        260        270        280        290        300 
DGPANNQAFT KVIYFHKGTI IKEEPLKGSA KHIEECSCYG HNQRVTCVCR DNWQGANRPV 

       310        320        330        340        350        360 
IEIDMNNLEH TSRYICTGVL TDTSRPKDKA IGECFNPITG SPGAPGIKGF GFLNENNTWL 

       370        380        390        400        410        420 
GRTISPKLRS GFEMLKIPNA GTDPDSKIKE RQEIVGNDNW SGYSGSFIDY WNDNSECYNP 

       430        440        450        460 
CFYVELIRGR PEEAKYVEWT SNSLIALCGS PIPVGSGSFP DGAQIKYFS 

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References

[1]"Genetic characterisation of an influenza A virus of unusual subtype (H1N7) isolated from pigs in England."
Brown I.H., Hill M.L., Harris P.A., Alexander D.J., McCauley J.W.
Arch. Virol. 142:1045-1050(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Large-scale sequence analysis of avian influenza isolates."
Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., Finkelstein D.B., Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., Webster R.G., Hoffmann E., Krauss S., Zheng J., Zhang Z., Naeve C.W.
Science 311:1576-1580(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Sequence variation at the 3' end of the neuraminidase gene from 39 influenza type A viruses."
Blok J.
(In) Nayak D., Fox C.F. (eds.); Genetic variation among influenza viruses, pp.45-54, University of California, Los Angeles (1982)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-88.
[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
U85989 mRNA. Translation: AAC57418.1.
CY005802 Genomic RNA. Translation: ABB20501.1.
K01008 Genomic RNA. Translation: AAA43411.1.

3D structure databases

ProteinModelPortalP88838.
SMRP88838. Positions 81-468.
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

PROP88838.

Entry information

Entry nameNRAM_I56A3
AccessionPrimary (citable) accession number: P88838
Secondary accession number(s): Q20P40, Q83983
Entry history
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: May 1, 1997
Last modified: February 19, 2014
This is version 78 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