Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9W7Y7 (NRAM_I97A1) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 81. 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

Protein attributes

Sequence length450 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.

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 caution

The sequence AAC34264.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 450450Neuraminidase
PRO_0000078700

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 3529Helical; Signal-anchor for type II membrane protein; Potential
Topological domain36 – 450415Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 7136Hypervariable stalk region By similarity
Region72 – 450379Head of neuraminidase By similarity

Sites

Active site1321 Potential
Active site2581 Potential
Active site3831 Potential
Metal binding2751Calcium; via carbonyl oxygen By similarity
Metal binding2791Calcium; via carbonyl oxygen By similarity
Metal binding3051Calcium By similarity
Binding site991Substrate Potential
Binding site2741Substrate Potential
Binding site3491Substrate Potential

Amino acid modifications

Glycosylation501N-linked (GlcNAc...); by host Potential
Glycosylation691N-linked (GlcNAc...); by host Potential
Glycosylation1271N-linked (GlcNAc...); by host Potential
Glycosylation2161N-linked (GlcNAc...); by host Potential
Disulfide bond73 ↔ 398 By similarity
Disulfide bond105 ↔ 110 By similarity
Disulfide bond165 ↔ 212 By similarity
Disulfide bond214 ↔ 219 By similarity
Disulfide bond260 ↔ 273 By similarity
Disulfide bond262 ↔ 271 By similarity
Disulfide bond299 ↔ 316 By similarity
Disulfide bond402 ↔ 427 By similarity

Experimental info

Sequence conflict441 – 4433GAD → DAE in AAC34264. Ref.2
Sequence conflict4431D → E in AAC32089. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q9W7Y7 [UniParc].

Last modified December 6, 2005. Version 2.
Checksum: 0DCB54FCB6E7C8F2

FASTA45049,503
        10         20         30         40         50         60 
MNPNQKIITI GSICMVVGII SLMLQIGNII SVWVSHIIQT WHPNQPEPCN QSINFYTEQA 

        70         80         90        100        110        120 
AASVTLAGNS SLCPISGWAI YSKDNSIRIG SKGDVFVIRE PFISCSHLEC RTFFLTQGAL 

       130        140        150        160        170        180 
LNDKHSNGTV KDRSPYRTLM SCPVGEAPSP YNSRFESVAW SASACHDGIS WLTIGISGPD 

       190        200        210        220        230        240 
NGAVAVLKYN GIITDTIKSW RNNILRTQES ECACVNGSCF TVMTDGPSNE QASYKIFKIE 

       250        260        270        280        290        300 
KGRVVKSVEL NAPNYHYEEC SCYPDAGEIT CVCRDNWHGS NRPWVSFNQN LEYQIGYICS 

       310        320        330        340        350        360 
GVFGDSPRPN DGTGSCGPVS LNGAYGVKGF SFKYGNGVWI GRTKSTSSRS GFEMIWDPNG 

       370        380        390        400        410        420 
WTETDSSFSL KQDIIAITDW SGYSGSFIQH PELTGLNCMR PCFWVELIRG RPKEKTIWTS 

       430        440        450 
GSSISFCGVN SDTVGWSWPD GADLPFTIDK 

« Hide

References

[1]"Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus."
Claas E.C.J., Osterhaus A.D., van Beek R., De Jong J.C., Rimmelzwaan G.F., Senne D.A., Krauss S., Shortridge K.F., Webster R.G.
Lancet 351:472-477(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness."
Subbarao K., Klimov A., Katz J., Regnery H., Lim W., Hall H., Perdue M., Swayne D., Bender C., Huang J., Hemphill M., Rowe T., Shaw M., Xu X., Fukuda K., Cox N.
Science 279:393-396(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong."
Suarez D.L., Perdue M.L., Cox N., Rowe T., Bender C., Huang J., Swayne D.E.
J. Virol. 72:6678-6688(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[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
AF028708 mRNA. Translation: AAC40507.1.
AF036357 Genomic RNA. Translation: AAC34264.1. Different initiation.
AF046089 Genomic RNA. Translation: AAC32089.1.

3D structure databases

ProteinModelPortalQ9W7Y7.
SMRQ9W7Y7. Positions 64-448.
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_I97A1
AccessionPrimary (citable) accession number: Q9W7Y7
Secondary accession number(s): O89527, Q9WA99
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: February 19, 2014
This is version 81 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