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Q8JSD9 (NRAM_I47A0) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 64. Feed History...

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

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.

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_0000280130

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 – 9055Hypervariable stalk region By similarity
Region91 – 469379Head of neuraminidase By similarity

Sites

Active site1511 Potential
Active site2771 Potential
Active site4021 Potential
Metal binding2941Calcium; via carbonyl oxygen By similarity
Metal binding2981Calcium; via carbonyl oxygen By similarity
Metal binding3241Calcium By similarity
Binding site1181Substrate Potential
Binding site2931Substrate Potential
Binding site3681Substrate Potential

Amino acid modifications

Glycosylation441N-linked (GlcNAc...); by host Potential
Glycosylation581N-linked (GlcNAc...); by host Potential
Glycosylation631N-linked (GlcNAc...); by host Potential
Glycosylation681N-linked (GlcNAc...); by host Potential
Glycosylation881N-linked (GlcNAc...); by host Potential
Glycosylation1461N-linked (GlcNAc...); by host Potential
Glycosylation2351N-linked (GlcNAc...); by host Potential
Glycosylation3651N-linked (GlcNAc...); by host Potential
Disulfide bond92 ↔ 417 By similarity
Disulfide bond124 ↔ 129 By similarity
Disulfide bond184 ↔ 231 By similarity
Disulfide bond233 ↔ 238 By similarity
Disulfide bond279 ↔ 292 By similarity
Disulfide bond281 ↔ 290 By similarity
Disulfide bond421 ↔ 446 By similarity

Natural variations

Natural variant68 – 725Missing in strain: A/Fort Monmouth/1/1947-MA.
Natural variant1301K → R in strain: A/Fort Monmouth/1/1947-MA.
Natural variant3391N → Y in strain: A/Fort Monmouth/1/1947-MA.
Natural variant3441D → N in strain: A/Fort Monmouth/1/1947-MA.
Natural variant3521R → K in strain: A/Fort Monmouth/1/1947-MA.
Natural variant3571G → V in strain: A/Fort Monmouth/1/1947-MA.
Natural variant3691K → Q in strain: A/Fort Monmouth/1/1947-MA.
Natural variant382 – 3832DP → ET in strain: A/Fort Monmouth/1/1947-MA.
Natural variant388 – 3892LV → FT in strain: A/Fort Monmouth/1/1947-MA.
Natural variant3931I → V in strain: A/Fort Monmouth/1/1947-MA.
Natural variant3961M → V in strain: A/Fort Monmouth/1/1947-MA.
Natural variant4601D → G in strain: A/Fort Monmouth/1/1947-MA.
Natural variant465 – 4662LN → FT in strain: A/Fort Monmouth/1/1947-MA.

Experimental info

Sequence conflict3651N → I in CAB40420. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8JSD9 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 74E0E3A8BB7F08BC

FASTA46951,499
        10         20         30         40         50         60 
MNPNQKIITI GSICMVVGII SLILQIGNIV SIWISHSIQT GNQNHTGTCD QSIITYKNST 

        70         80         90        100        110        120 
WVNQTYVNIS NTNVVAGKDT TSVILAGNSS LCPIRGWAIY SKDNGVRIGS KGDVFVIREP 

       130        140        150        160        170        180 
FISCSHLECK TFFLTQGALL NDKHSNGTVK DRSPYRALMS CPVGEAPSPY NSRFESVAWS 

       190        200        210        220        230        240 
ASACHDGMGW LTIGISGPDD GAVAVLKYNG IITETIKSWR KEILRTQESE CVCVNGSCFT 

       250        260        270        280        290        300 
IMTDGPSGGP ASYKIFKIEK GKVTKSIELD APNSHYEECS CYPDTSKVMC VCRDNWHGSN 

       310        320        330        340        350        360 
RPWVSFDQNL DYQMGYICSG VFGDNPRPKD GKGSCGPVNV DGADGVKGFS YRYGNGGWIG 

       370        380        390        400        410        420 
RTKSNSSRKG FEMIWDPNGW TDPDSNFLVK QDIVAMTDWS GYSGSFVQHP ELTGLDCMRP 

       430        440        450        460 
CFWVELIRGR PKENTIWTSG SSISFCGVNS DTVDWSWPDD AELPLNIDK 

« Hide

References

[1]"Genetic analysis of mouse-adapted influenza A virus identifies roles for the NA, PB1, and PB2 genes in virulence."
Brown E.G., Bailly J.E.
Virus Res. 61:63-76(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: A/Fort Monmouth/1/1947-MA.
[2]"Characterization of the 1918 'Spanish' influenza virus neuraminidase gene."
Reid A.H., Fanning T.G., Janczewski T.A., Taubenberger J.K.
Proc. Natl. Acad. Sci. U.S.A. 97:6785-6790(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: A/Fort Monmouth/1/1947-MA.
[3]"The total influenza vaccine failure of 1947 revisited: major intrasubtypic antigenic change can explain failure of vaccine in a post-World War II epidemic."
Kilbourne E.D., Smith C., Brett I., Pokorny B.A., Johansson B., Cox N.
Proc. Natl. Acad. Sci. U.S.A. 99:10748-10752(2002) [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
AF494253 Genomic RNA. Translation: AAM76693.1.
Y14193 Genomic RNA. Translation: CAB40419.1.
Y14194 Genomic RNA. Translation: CAB40420.1.
AF250357 mRNA. Translation: AAF77037.1.

3D structure databases

ProteinModelPortalQ8JSD9.
SMRQ8JSD9. Positions 83-467.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

CAZyGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKQ8JSD9.

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_I47A0
AccessionPrimary (citable) accession number: Q8JSD9
Secondary accession number(s): Q9WMK7, Q9WMK8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: October 1, 2002
Last modified: February 19, 2014
This is version 64 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