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P03480 (NRAM_I49A1) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 93. 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/Duck/Germany/1949 H10N7) [Complete proteome]
Taxonomic identifier382838 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]

Protein attributes

Sequence length471 AA.
Sequence statusComplete.
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 – 471471Neuraminidase
PRO_0000078685

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 2721Helical; Signal-anchor for type II membrane protein; Potential
Topological domain28 – 471444Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 8954Hypervariable stalk region By similarity
Region90 – 471382Head of neuraminidase By similarity

Sites

Active site1501 Potential
Active site2761 Potential
Active site4051 Potential
Metal binding2931Calcium; via carbonyl oxygen By similarity
Metal binding2971Calcium; via carbonyl oxygen By similarity
Metal binding3241Calcium By similarity
Binding site1171Substrate Potential
Binding site2921Substrate Potential
Binding site3711Substrate Potential

Amino acid modifications

Glycosylation321N-linked (GlcNAc...); by host Potential
Glycosylation471N-linked (GlcNAc...); by host Potential
Glycosylation561N-linked (GlcNAc...); by host Potential
Glycosylation571N-linked (GlcNAc...); by host Potential
Glycosylation671N-linked (GlcNAc...); by host Potential
Glycosylation681N-linked (GlcNAc...); by host Potential
Glycosylation871N-linked (GlcNAc...); by host Potential
Glycosylation1451N-linked (GlcNAc...); by host Potential
Glycosylation2001N-linked (GlcNAc...); by host Potential
Glycosylation2341N-linked (GlcNAc...); by host Potential
Glycosylation4011N-linked (GlcNAc...); by host Potential
Disulfide bond91 ↔ 419 By similarity
Disulfide bond123 ↔ 128 By similarity
Disulfide bond183 ↔ 230 By similarity
Disulfide bond232 ↔ 237 By similarity
Disulfide bond278 ↔ 291 By similarity
Disulfide bond280 ↔ 289 By similarity
Disulfide bond423 ↔ 450 By similarity

Experimental info

Sequence conflict881K → H in AAA43391. Ref.2
Sequence conflict881K → H in AAA43357. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P03480 [UniParc].

Last modified March 6, 2007. Version 2.
Checksum: 68F6BBACFCDD21A1

FASTA47151,800
        10         20         30         40         50         60 
MNPNQKLFAL SGVAIALSVM NLLIGISNVG LNVSLHLKEK GTKQEENLTC TTITQNNTTV 

        70         80         90        100        110        120 
VENTYVNNTT IITKEPDLKA PSYLLLNKSL CSVEGWVVIA KDNAIRFGES EQIIVTREPY 

       130        140        150        160        170        180 
VSCDPSGCKM YALHQGTTIR NKHSNGTIHD RTAFRGLIST PLGTPPTVSN SDFICVGWSS 

       190        200        210        220        230        240 
TSCHDGVGRM TICIQGNNDN ATATVYYNRR LTTTIKPWAR NILRTQESEC VCHNGTCAVV 

       250        260        270        280        290        300 
MTDGSASSQA YTKVMYFHKG LVIKEEPLKG SAKHIEECSC YGHNQKITCV CRDNWQGANR 

       310        320        330        340        350        360 
PIIEIDMNTL EHTSRYVCTG ILTDTSRPGD KPSGDCSNPI TGSPSAPGVK GFGFLNGDNT 

       370        380        390        400        410        420 
WLGRTISPRS RSGFEMLKIP NAGTDPNSRI AERQEIVDNN NWSGYSGSFI DYWDDDNECY 

       430        440        450        460        470 
NPCFYVELIR GRPEEAKYVW WTSNSLIALC GSPFPVGSGS FPDGAQIQYF S 

« Hide

References

[1]"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].
[2]"Variation in the membrane-insertion and 'stalk' sequences in eight subtypes of influenza type A virus neuraminidase."
Blok J., Air G.M.
Biochemistry 21:4001-4007(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-96.
[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 1-96.
[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
CY014673 Genomic RNA. Translation: ABI84537.1.
J02099 Genomic RNA. Translation: AAA43391.1.
K01022 Genomic RNA. Translation: AAA43357.1.

3D structure databases

ProteinModelPortalP03480.
SMRP03480. Positions 82-470.
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_I49A1
AccessionPrimary (citable) accession number: P03480
Secondary accession number(s): Q0A445, Q6LEJ3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 6, 2007
Last modified: February 19, 2014
This is version 93 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