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P03468 (NRAM_I34A1) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. 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/Puerto Rico/8/1934 H1N1) [Reference proteome]
Taxonomic identifier211044 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length454 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.

Ontologies

Keywords
   Cellular componentHost cell membrane
Host membrane
Membrane
Virion
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   Molecular functionGlycosidase
Hydrolase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactive induction of host immune response by virus

Traceable author statement. Source: Reactome

carbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

fusion of virus membrane with host plasma membrane

Traceable author statement. Source: Reactome

intracellular transport of viral protein in host cell

Traceable author statement. Source: Reactome

modulation by virus of host morphology or physiology

Traceable author statement. Source: Reactome

receptor-mediated endocytosis of virus by host cell

Traceable author statement. Source: Reactome

uncoating of virus

Traceable author statement. Source: Reactome

viral entry into host cell

Traceable author statement. Source: Reactome

viral genome packaging

Traceable author statement. Source: Reactome

viral life cycle

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

viral release from host cell

Traceable author statement. Source: Reactome

viral transcription

Traceable author statement. Source: Reactome

virion assembly

Traceable author statement. Source: Reactome

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

endosome lumen

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

host cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

virion membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionexo-alpha-(2->3)-sialidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

exo-alpha-(2->6)-sialidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

exo-alpha-(2->8)-sialidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 454454Neuraminidase
PRO_0000078712

Regions

Topological domain1 – 66Intravirion Potential
Transmembrane7 – 3529Helical; Signal-anchor for type II membrane protein; Potential
Topological domain36 – 454419Virion surface Potential
Region11 – 3323Involved in apical transport and lipid raft association By similarity
Region36 – 7540Hypervariable stalk region
Region76 – 454379Head of neuraminidase

Sites

Active site1361 Potential
Active site2621 Potential
Active site3871 Potential
Metal binding2791Calcium; via carbonyl oxygen By similarity
Metal binding2831Calcium; via carbonyl oxygen By similarity
Metal binding3091Calcium By similarity
Metal binding3291Calcium; via carbonyl oxygen By similarity
Binding site1031Substrate Potential
Binding site2781Substrate Potential
Binding site3531Substrate Potential

Amino acid modifications

Glycosylation441N-linked (GlcNAc...); by host Potential
Glycosylation581N-linked (GlcNAc...); by host Potential
Glycosylation731N-linked (GlcNAc...); by host Potential
Glycosylation1311N-linked (GlcNAc...); by host Potential
Glycosylation2201N-linked (GlcNAc...); by host Potential
Disulfide bond77 ↔ 402 By similarity
Disulfide bond109 ↔ 114 By similarity
Disulfide bond169 ↔ 216 By similarity
Disulfide bond218 ↔ 223 By similarity
Disulfide bond264 ↔ 277 By similarity
Disulfide bond266 ↔ 275 By similarity
Disulfide bond303 ↔ 320 By similarity
Disulfide bond406 ↔ 431 By similarity

Experimental info

Sequence conflict81I → T in AAM75160. Ref.2
Sequence conflict511Q → H in AAA43415. Ref.5
Sequence conflict1281K → R in AAA43412. Ref.1
Sequence conflict1311N → S in ABO21711. Ref.3
Sequence conflict1311N → S in ABD77678. Ref.4
Sequence conflict3141E → K in AAA43412. Ref.1
Sequence conflict4031M → I in AAA43412. Ref.1
Sequence conflict4511S → T in AAA43412. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P03468 [UniParc].

Last modified March 6, 2007. Version 2.
Checksum: 7C52E0A9FD93A98B

FASTA45450,121
        10         20         30         40         50         60 
MNPNQKIITI GSICLVVGLI SLILQIGNII SIWISHSIQT GSQNHTGICN QNIITYKNST 

        70         80         90        100        110        120 
WVKDTTSVIL TGNSSLCPIR GWAIYSKDNS IRIGSKGDVF VIREPFISCS HLECRTFFLT 

       130        140        150        160        170        180 
QGALLNDKHS NGTVKDRSPY RALMSCPVGE APSPYNSRFE SVAWSASACH DGMGWLTIGI 

       190        200        210        220        230        240 
SGPDNGAVAV LKYNGIITET IKSWRKKILR TQESECACVN GSCFTIMTDG PSDGLASYKI 

       250        260        270        280        290        300 
FKIEKGKVTK SIELNAPNSH YEECSCYPDT GKVMCVCRDN WHGSNRPWVS FDQNLDYQIG 

       310        320        330        340        350        360 
YICSGVFGDN PRPEDGTGSC GPVYVDGANG VKGFSYRYGN GVWIGRTKSH SSRHGFEMIW 

       370        380        390        400        410        420 
DPNGWTETDS KFSVRQDVVA MTDWSGYSGS FVQHPELTGL DCMRPCFWVE LIRGRPKEKT 

       430        440        450 
IWTSASSISF CGVNSDTVDW SWPDGAELPF SIDK 

« Hide

References

[1]"Structure of the neuraminidase gene in human influenza virus A/PR/8/34."
Fields S., Winter G., Brownlee G.G.
Nature 290:213-217(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Plasmid-only rescue of influenza A virus vaccine candidates."
Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L., Garcia-Sastre A., Palese P.
Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments."
de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M.
Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
[4]"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].
[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 1-71.
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02146 Genomic RNA. Translation: AAA43412.1.
AF389120 Genomic RNA. Translation: AAM75160.1.
EF467823 Genomic RNA. Translation: ABO21711.1.
CY009446 Genomic RNA. Translation: ABD77678.1.
K01031 Genomic RNA. Translation: AAA43415.1.
RefSeqNP_040981.1. NC_002018.1.

3D structure databases

ProteinModelPortalP03468.
SMRP03468. Positions 68-452.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP03468. 6 interactions.

Chemistry

BindingDBP03468.
ChEMBLCHEMBL2051.

Protein family/group databases

CAZyGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID956530.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.
SABIO-RKP03468.

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_I34A1
AccessionPrimary (citable) accession number: P03468
Secondary accession number(s): A4GXH6 expand/collapse secondary AC list , Q20N35, Q84043, Q8JUU4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 6, 2007
Last modified: April 16, 2014
This is version 108 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