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P03468

- NRAM_I34A1

UniProt

P03468 - NRAM_I34A1

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 2 (06 Mar 2007)
      Previous versions | rss
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    Functioni

    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 activityi

    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.

    Cofactori

    Binds 1 calcium ion per subunit.By similarity

    Enzyme regulationi

    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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei103 – 1031SubstrateBy similarity
    Active sitei136 – 1361Proton donor/acceptorBy similarity
    Binding sitei137 – 1371SubstrateBy similarity
    Binding sitei278 – 2781SubstrateBy similarity
    Metal bindingi279 – 2791Calcium; via carbonyl oxygenBy similarity
    Metal bindingi283 – 2831Calcium; via carbonyl oxygenBy similarity
    Metal bindingi309 – 3091CalciumBy similarity
    Metal bindingi329 – 3291Calcium; via carbonyl oxygenBy similarity
    Binding sitei353 – 3531SubstrateBy similarity
    Active sitei387 – 3871NucleophileBy similarity

    GO - Molecular functioni

    1. exo-alpha-(2->3)-sialidase activity Source: UniProtKB-EC
    2. exo-alpha-(2->6)-sialidase activity Source: UniProtKB-EC
    3. exo-alpha-(2->8)-sialidase activity Source: UniProtKB-EC
    4. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. active induction of host immune response by virus Source: Reactome
    2. carbohydrate metabolic process Source: InterPro
    3. fusion of virus membrane with host plasma membrane Source: Reactome
    4. intracellular transport of viral protein in host cell Source: Reactome
    5. modulation by virus of host morphology or physiology Source: Reactome
    6. receptor-mediated endocytosis of virus by host cell Source: Reactome
    7. uncoating of virus Source: Reactome
    8. viral entry into host cell Source: Reactome
    9. viral genome packaging Source: Reactome
    10. viral life cycle Source: Reactome
    11. viral process Source: Reactome
    12. viral release from host cell Source: Reactome
    13. viral transcription Source: Reactome
    14. virion assembly Source: Reactome

    Keywords - Molecular functioni

    Glycosidase, Hydrolase

    Keywords - Ligandi

    Calcium, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_6145. Influenza Life Cycle.
    REACT_6147. Entry of Influenza Virion into Host Cell via Endocytosis.
    REACT_6212. Budding.
    REACT_6213. Influenza Virus Induced Apoptosis.
    REACT_6215. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
    REACT_6235. Packaging of Eight RNA Segments.
    REACT_6277. Assembly of Viral Components at the Budding Site.
    REACT_6321. Uncoating of the Influenza Virion.
    REACT_6326. Release.
    REACT_6351. Fusion of the Influenza Virion to the Host Cell Endosome.
    REACT_9491. Viral mRNA Translation.
    SABIO-RKP03468.

    Protein family/group databases

    CAZyiGH34. Glycoside Hydrolase Family 34.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Neuraminidase (EC:3.2.1.18)
    Gene namesi
    Name:NA
    OrganismiInfluenza A virus (strain A/Puerto Rico/8/1934 H1N1)
    Taxonomic identifieri211044 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Homo sapiens (Human) [TaxID: 9606]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000009255: Genome

    Subcellular locationi

    Virion membrane By similarity. Host apical cell membrane By similarity; 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.By similarity

    GO - Cellular componenti

    1. endocytic vesicle membrane Source: Reactome
    2. endoplasmic reticulum membrane Source: Reactome
    3. endosome lumen Source: Reactome
    4. extracellular region Source: Reactome
    5. Golgi membrane Source: Reactome
    6. host cell plasma membrane Source: UniProtKB-SubCell
    7. integral component of membrane Source: UniProtKB-KW
    8. plasma membrane Source: Reactome
    9. virion membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host cell membrane, Host membrane, Membrane, Virion

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 454454NeuraminidasePRO_0000078712Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi44 – 441N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi58 – 581N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi73 – 731N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi77 ↔ 402By similarity
    Disulfide bondi109 ↔ 114By similarity
    Glycosylationi131 – 1311N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi169 ↔ 216By similarity
    Disulfide bondi218 ↔ 223By similarity
    Glycosylationi220 – 2201N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi264 ↔ 277By similarity
    Disulfide bondi266 ↔ 275By similarity
    Disulfide bondi303 ↔ 320By similarity
    Disulfide bondi406 ↔ 431By similarity

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.By similarity

    Protein-protein interaction databases

    IntActiP03468. 6 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP03468.
    SMRiP03468. Positions 68-452.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66IntravirionSequence Analysis
    Topological domaini36 – 454419Virion surfaceSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei7 – 3529Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni11 – 3323Involved in apical transport and lipid raft associationBy similarityAdd
    BLAST
    Regioni36 – 7540Hypervariable stalk regionAdd
    BLAST
    Regioni76 – 454379Head of neuraminidaseAdd
    BLAST
    Regioni262 – 2632Substrate bindingBy similarity

    Domaini

    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.By similarity

    Sequence similaritiesi

    Belongs to the glycosyl hydrolase 34 family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Family and domain databases

    Gene3Di2.120.10.10. 1 hit.
    InterProiIPR001860. Glyco_hydro_34.
    IPR011040. Sialidases.
    [Graphical view]
    PfamiPF00064. Neur. 1 hit.
    [Graphical view]
    SUPFAMiSSF50939. SSF50939. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P03468-1 [UniParc]FASTAAdd to Basket

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    MNPNQKIITI GSICLVVGLI SLILQIGNII SIWISHSIQT GSQNHTGICN    50
    QNIITYKNST WVKDTTSVIL TGNSSLCPIR GWAIYSKDNS IRIGSKGDVF 100
    VIREPFISCS HLECRTFFLT QGALLNDKHS NGTVKDRSPY RALMSCPVGE 150
    APSPYNSRFE SVAWSASACH DGMGWLTIGI SGPDNGAVAV LKYNGIITET 200
    IKSWRKKILR TQESECACVN GSCFTIMTDG PSDGLASYKI FKIEKGKVTK 250
    SIELNAPNSH YEECSCYPDT GKVMCVCRDN WHGSNRPWVS FDQNLDYQIG 300
    YICSGVFGDN PRPEDGTGSC GPVYVDGANG VKGFSYRYGN GVWIGRTKSH 350
    SSRHGFEMIW DPNGWTETDS KFSVRQDVVA MTDWSGYSGS FVQHPELTGL 400
    DCMRPCFWVE LIRGRPKEKT IWTSASSISF CGVNSDTVDW SWPDGAELPF 450
    SIDK 454
    Length:454
    Mass (Da):50,121
    Last modified:March 6, 2007 - v2
    Checksum:i7C52E0A9FD93A98B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti8 – 81I → T in AAM75160. (PubMed:11779399)Curated
    Sequence conflicti51 – 511Q → H in AAA43415. (PubMed:6927853)Curated
    Sequence conflicti128 – 1281K → R in AAA43412. (PubMed:7010182)Curated
    Sequence conflicti131 – 1311N → S in ABO21711. (PubMed:15163504)Curated
    Sequence conflicti131 – 1311N → S in ABD77678. 1 PublicationCurated
    Sequence conflicti314 – 3141E → K in AAA43412. (PubMed:7010182)Curated
    Sequence conflicti403 – 4031M → I in AAA43412. (PubMed:7010182)Curated
    Sequence conflicti451 – 4511S → T in AAA43412. (PubMed:7010182)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    RefSeqiNP_040981.1. NC_002018.1.

    Genome annotation databases

    GeneIDi956530.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    RefSeqi NP_040981.1. NC_002018.1.

    3D structure databases

    ProteinModelPortali P03468.
    SMRi P03468. Positions 68-452.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P03468. 6 interactions.

    Chemistry

    BindingDBi P03468.
    ChEMBLi CHEMBL2051.

    Protein family/group databases

    CAZyi GH34. Glycoside Hydrolase Family 34.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 956530.

    Enzyme and pathway databases

    Reactomei REACT_6145. Influenza Life Cycle.
    REACT_6147. Entry of Influenza Virion into Host Cell via Endocytosis.
    REACT_6212. Budding.
    REACT_6213. Influenza Virus Induced Apoptosis.
    REACT_6215. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
    REACT_6235. Packaging of Eight RNA Segments.
    REACT_6277. Assembly of Viral Components at the Budding Site.
    REACT_6321. Uncoating of the Influenza Virion.
    REACT_6326. Release.
    REACT_6351. Fusion of the Influenza Virion to the Host Cell Endosome.
    REACT_9491. Viral mRNA Translation.
    SABIO-RK P03468.

    Family and domain databases

    Gene3Di 2.120.10.10. 1 hit.
    InterProi IPR001860. Glyco_hydro_34.
    IPR011040. Sialidases.
    [Graphical view ]
    Pfami PF00064. Neur. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50939. SSF50939. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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. 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. 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.

    Entry informationi

    Entry nameiNRAM_I34A1
    AccessioniPrimary (citable) accession number: P03468
    Secondary accession number(s): A4GXH6
    , Q20N35, Q84043, Q8JUU4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: March 6, 2007
    Last modified: October 1, 2014
    This is version 110 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    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.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Glycosyl hydrolases
      Classification of glycosyl hydrolase families and list of entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3