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Q2LFV4 (NRAM_I05A1) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 45. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Protein attributes

Sequence length441 AA.
Sequence statusFragment.
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

Chain‹1 – ›441›441Neuraminidase
PRO_0000310943

Regions

Topological domain‹1 – 4›4Intravirion Potential
Transmembrane5 – 2521Helical; Potential
Topological domain26 – ›441›416Virion surface Potential
Region3 – 2523Involved in apical transport and lipid raft association By similarity
Region28 – 6235Hypervariable stalk region By similarity
Region63 – ›441›379Head of neuraminidase By similarity

Sites

Active site1231 Potential
Active site2491 Potential
Active site3741 Potential
Metal binding2661Calcium; via carbonyl oxygen By similarity
Metal binding2701Calcium; via carbonyl oxygen By similarity
Metal binding2961Calcium By similarity
Binding site901Substrate Potential
Binding site2651Substrate Potential
Binding site3401Substrate Potential

Amino acid modifications

Glycosylation601N-linked (GlcNAc...); by host Potential
Glycosylation1181N-linked (GlcNAc...); by host Potential
Glycosylation2071N-linked (GlcNAc...); by host Potential
Disulfide bond64 ↔ 389 By similarity
Disulfide bond96 ↔ 101 By similarity
Disulfide bond156 ↔ 203 By similarity
Disulfide bond205 ↔ 210 By similarity
Disulfide bond251 ↔ 264 By similarity
Disulfide bond253 ↔ 262 By similarity
Disulfide bond393 ↔ 418 By similarity

Experimental info

Non-terminal residue11
Non-terminal residue4411

Sequences

Sequence LengthMass (Da)Tools
Q2LFV4 [UniParc].

Last modified February 21, 2006. Version 1.
Checksum: 93581D0C7DBA5951

FASTA44148,204
        10         20         30         40         50         60 
TIGSICMVIG IVSLMLQIGN MISIWVSHSI QTGNQNQVEP ISNTNFLTEK AVASVTLAGN 

        70         80         90        100        110        120 
SSLCPIRGWA VHSKDNSIRI GSKGDVFVIR EPFISCSHLE CRTFFLTQGA LLNDKHSNGT 

       130        140        150        160        170        180 
VKDRSPHRTL MSCPVGEAPS PYNSRFESVA WSASACHDGT SWLTIGISGP DNGAVAVLKY 

       190        200        210        220        230        240 
NGMITDTIKS WRNNILRTQE SECACVNGSC FTVMTDGPSN GQASYKIFKM EKGKVVKSVE 

       250        260        270        280        290        300 
LDAPNYHYEE CSCYPDAGEI TCVCRDNWHG SNRPWVSFNQ NLEYQIGYIC SGVFGDNPRP 

       310        320        330        340        350        360 
NDGTGSCGPV SPNGAYGVKG FSFKYGNGVW IGRTKSPNSR SGFEMIWDPN GWTETDSSFS 

       370        380        390        400        410        420 
VKQDIVAITD WSGYSGSFVQ HPELTGLDCI RPCFWVELIR GRPKESTIWT SGSSISFCGV 

       430        440 
NSDTVSWSWP DGAELPFTID K 

« Hide

References

[1]"Emergence and predominance of an H5N1 influenza variant in China."
Smith G.J., Fan X.H., Wang J., Li K.S., Qin K., Zhang J.X., Vijaykrishna D., Cheung C.L., Huang K., Rayner J.M., Peiris J.S., Chen H., Webster R.G., Guan Y.
Proc. Natl. Acad. Sci. U.S.A. 103:16936-16941(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
DQ321028 Genomic RNA. Translation: ABC66670.1.

3D structure databases

ProteinModelPortalQ2LFV4.
SMRQ2LFV4. Positions 55-439.
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_I05A1
AccessionPrimary (citable) accession number: Q2LFV4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: February 21, 2006
Last modified: February 19, 2014
This is version 45 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