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Q67344 (NRAM_I82A7) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 76. 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/Swine/Hong Kong/127/1982 H3N2)
Taxonomic identifier384483 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length446 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

Chain1 – 446446Neuraminidase
PRO_0000280158

Regions

Region13 – 6755Hypervariable stalk region By similarity
Region68 – 446379Head of neuraminidase By similarity
Compositional bias308 – 3125Poly-Ser

Sites

Active site1281 Potential
Active site2531 Potential
Active site3831 Potential
Metal binding2701Calcium; via carbonyl oxygen By similarity
Metal binding2741Calcium; via carbonyl oxygen By similarity
Metal binding3011Calcium By similarity
Binding site951Substrate Potential
Binding site2691Substrate Potential
Binding site3481Substrate Potential

Amino acid modifications

Glycosylation381N-linked (GlcNAc...); by host Potential
Glycosylation471N-linked (GlcNAc...); by host Potential
Glycosylation631N-linked (GlcNAc...); by host Potential
Glycosylation1231N-linked (GlcNAc...); by host Potential
Glycosylation1771N-linked (GlcNAc...); by host Potential
Glycosylation2111N-linked (GlcNAc...); by host Potential
Glycosylation3791N-linked (GlcNAc...); by host Potential
Disulfide bond69 ↔ 394 By similarity
Disulfide bond101 ↔ 106 By similarity
Disulfide bond160 ↔ 207 By similarity
Disulfide bond209 ↔ 214 By similarity
Disulfide bond255 ↔ 268 By similarity
Disulfide bond257 ↔ 266 By similarity
Disulfide bond295 ↔ 314 By similarity
Disulfide bond398 ↔ 424 By similarity

Experimental info

Non-terminal residue11

Sequences

Sequence LengthMass (Da)Tools
Q67344 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: B3E31B09E6728A9D

FASTA44649,915
        10         20         30         40         50         60 
MQIAILVTTV TLHFNQYECD SLADNQVMPC EPIIIERNIT EIIYLTNTTI EKEICPKLME 

        70         80         90        100        110        120 
YRNWSRPQCK ITGFAPFSKD NSIRLSAGGD IWVTREPYVS CDPGKCYQFA LGQGTTLDNK 

       130        140        150        160        170        180 
HSNDTIHDRI PHRTLLMNEL GVPFHLGTRQ VCIAWSSSSC HDGKAWLHVC VTGDDKNATA 

       190        200        210        220        230        240 
SFIYDGRLVD SMGSWSQNIL RTQESECVCI NGTCTVVMTD GSASGRADTR ILFIEEGKIV 

       250        260        270        280        290        300 
HISPLSGSAQ HVEECSCYPR YPSVRCICRD NWKGSNRPIV DINIKDYSID SRYVCSGLVG 

       310        320        330        340        350        360 
DTPRNNDRSS SSDCKNPNND KGNHGVKGWA FDDGNDVWMG RTISKDSRSG YETFKVIDGW 

       370        380        390        400        410        420 
STPNSKSQIN RQVIVDRDNR SGYSGIFSVE SKGCINRCFY VELIRGRKQE TRVWWTSSSI 

       430        440 
VVFCGTSGTY GKGSWPDGAN INFMPI 

« Hide

References

[1]"Genetic analysis of porcine H3N2 viruses originating in Southern China."
Nerome K., Kanegae Y., Shortridge K.F., Sugita S., Ishida M.
J. Gen. Virol. 76:613-624(1995) [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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D21194 Genomic RNA. Translation: BAA04730.1.

3D structure databases

ProteinModelPortalQ67344.
SMRQ67344. Positions 59-446.
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_I82A7
AccessionPrimary (citable) accession number: Q67344
Entry history
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: November 1, 1996
Last modified: February 19, 2014
This is version 76 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