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P03469 (NRAM_I77AB) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 98. 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/USSR/90/1977 H1N1) [Complete proteome]
Taxonomic identifier381516 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length470 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 – 470470Neuraminidase
PRO_0000078723

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 3529Helical; Signal-anchor for type II membrane protein; Potential
Topological domain36 – 470435Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 9055Hypervariable stalk region
Region91 – 470380Head of neuraminidase

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
Glycosylation4551N-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 bond318 ↔ 335 By similarity
Disulfide bond421 ↔ 447 By similarity

Experimental info

Sequence conflict481I → T in AAA43420. Ref.4
Sequence conflict481I → T in AAA43447. Ref.5
Sequence conflict511Q → H in AAA43420. Ref.4
Sequence conflict511Q → H in AAA43447. Ref.5
Sequence conflict1851H → Y in AAA43449. Ref.1
Sequence conflict1901W → C in AAA43449. Ref.1
Sequence conflict3341S → R in AAA43449. Ref.1
Sequence conflict3571V → G in AAA43449. Ref.1
Sequence conflict3831T → P in AAA43449. Ref.1
Sequence conflict3931V → I in AAA43449. Ref.1
Sequence conflict4051S → R in AAA43449. Ref.1
Sequence conflict4611G → D in AAA43449. Ref.1
Sequence conflict4661F → L in AAA43449. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P03469 [UniParc].

Last modified March 6, 2007. Version 2.
Checksum: E3578AC6519D0266

FASTA47051,863
        10         20         30         40         50         60 
MNPNQKIITI GSICMAIGII SLILQIGNII SIWVSHSIQT GSQNHTGICN QRIITYENST 

        70         80         90        100        110        120 
WVNQTYVNIS NTNVVAGKDT TSMTLAGNSS LCPIRGWAIY SKDNSIRIGS KGDVFVIREP 

       130        140        150        160        170        180 
FISCSHLECR TFFLTQGALL NDKHSNGTVK DRSPYRALMS CPIGEAPSPY NSRFESVAWS 

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

       250        260        270        280        290        300 
IMTDGPSDGP ASYRIFKIEK GKITKSIELD APNSHYEECS CYPDTGTVMC VCRDNWHGSN 

       310        320        330        340        350        360 
RPWVSFNQNL DYQIGYICSG VFGDNPRPKD GKGSCDPVNV DGADGVKGFS YRYGNGVWIG 

       370        380        390        400        410        420 
RTKSNSSRKG FEMIWDPNGW TDTDSNFLVK QDVVAMTDWS GYSGSFVQHP ELTGLDCMRP 

       430        440        450        460        470 
CFWVELIRGR PREKTTIWTS GSSISFCGVN SDTVNWSWPD GAELPFTIDK 

« Hide

References

[1]"Nucleotide sequence of the influenza virus A/USSR/90/77 neuraminidase gene."
Concannon P., Kwolek C.J., Salser W.A.
J. Virol. 50:654-656(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"The NIAID influenza genome sequencing project."
Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y. expand/collapse author list , Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Complete genome sequencing and analysis of selected influenza virus vaccine strains spanning six decades (1933-1999)."
Mbawuike I.N., Zhang Y., Yamada R.E., Nino D., Bui H.-H., Sette A., Couch R.B.
Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[4]"Block deletions in the neuraminidase genes from some influenza A viruses of the N1 subtype."
Blok J., Air G.M.
Virology 118:229-234(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 41-86.
[5]"Sequence variation at the 3' end of the neuraminidase gene from 39 influenza type A viruses."
Blok J., Air G.M.
Virology 121:211-229(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-86.
[6]"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.
[7]"Neuraminidase inhibitors for influenza."
Moscona A.
N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[8]"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
K02018 Genomic RNA. Translation: AAA43449.1.
CY010374 Genomic RNA. Translation: ABD95353.1.
DQ508899 Genomic RNA. Translation: ABF21333.1.
J02564 Genomic RNA. Translation: AAA43420.1.
K01038 Genomic RNA. Translation: AAA43447.1.

3D structure databases

ProteinModelPortalP03469.
SMRP03469. Positions 85-468.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

CAZyGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKP03469.

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_I77AB
AccessionPrimary (citable) accession number: P03469
Secondary accession number(s): Q1WP06, Q83958, Q83959
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 6, 2007
Last modified: February 19, 2014
This is version 98 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