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P03470

- NRAM_I33A0

UniProt

P03470 - NRAM_I33A0

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 2 (20 Dec 2005)
      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.1 Publication
    Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious.1 Publication

    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 sitei102 – 1021SubstrateBy similarity
    Active sitei135 – 1351Proton donor/acceptorBy similarity
    Binding sitei136 – 1361SubstrateBy similarity
    Binding sitei277 – 2771SubstrateBy similarity
    Metal bindingi278 – 2781Calcium; via carbonyl oxygenBy similarity
    Metal bindingi282 – 2821Calcium; via carbonyl oxygenBy similarity
    Metal bindingi308 – 3081CalciumBy similarity
    Metal bindingi328 – 3281Calcium; via carbonyl oxygenBy similarity
    Binding sitei352 – 3521SubstrateBy similarity
    Active sitei386 – 3861NucleophileBy 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. carbohydrate metabolic process Source: InterPro

    Keywords - Molecular functioni

    Glycosidase, Hydrolase

    Keywords - Ligandi

    Calcium, Metal-binding

    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/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
    Taxonomic identifieri381518 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Homo sapiens (Human) [TaxID: 9606]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000000834: Genome

    Subcellular locationi

    Virion membrane 1 Publication. Host apical cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication
    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.

    GO - Cellular componenti

    1. host cell plasma membrane Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. 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 – 453453NeuraminidasePRO_0000078726Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi44 – 441N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi72 – 721N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi76 ↔ 401By similarity
    Disulfide bondi108 ↔ 113By similarity
    Glycosylationi130 – 1301N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi168 ↔ 215By similarity
    Disulfide bondi217 ↔ 222By similarity
    Glycosylationi219 – 2191N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi263 ↔ 276By similarity
    Disulfide bondi265 ↔ 274By similarity
    Disulfide bondi302 ↔ 319By similarity
    Disulfide bondi405 ↔ 430By similarity

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.

    Structurei

    3D structure databases

    ProteinModelPortaliP03470.
    SMRiP03470. Positions 67-451.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66IntravirionSequence Analysis
    Topological domaini36 – 453418Virion 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 associationAdd
    BLAST
    Regioni36 – 7439Hypervariable stalk regionAdd
    BLAST
    Regioni75 – 453379Head of neuraminidaseAdd
    BLAST
    Regioni261 – 2622Substrate 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.

    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.

    P03470-1 [UniParc]FASTAAdd to Basket

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    MNPNQKIITI GSICMVVGII SLILQIGNII SIWISHSIQT GNQNHTGICN    50
    QGIITYNVVA GQDSTSVILT GNSSLCPIRG WAIHSKDNGI RIGSKGDVFV 100
    IREPFISCSH LECRTFFLTQ GALLNDKHSN GTVKDRSPYR ALMSCPVGEA 150
    PSPYNSRFES VAWSASACHD GMGWLTIGIS GPDNGAVAVL KYNGIITETI 200
    KSWRKKILRT QESECTCVNG SCFTIMTDGP SNGLASYKIF KIEKGKVTKS 250
    IELNAPNSHY EECSCYPDTG KVMCVCRDNW HGSNRPWVSF DQNLDYQIGY 300
    ICSGVFGDNP RPKDGPGSCG PVSADGANGV KGFSYRYGNG VWIGRTKSDS 350
    SRHGFEMIWD PNGWTETDSR FSVRQDVVAM TDRSGYSGSF VQHPELTGLD 400
    CMRPCFWVEL IRGRPEEETI WTSGSIISFC GVNSDTVDWS WPDGAELPFT 450
    IDK 453
    Length:453
    Mass (Da):49,687
    Last modified:December 20, 2005 - v2
    Checksum:i76E63E3A97D1EFEC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti172 – 1721M → V in AAA43397. (PubMed:7077751)Curated
    Sequence conflicti380 – 3823MTD → ITN in AAA43397. (PubMed:7077751)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti53 – 531I → S in strain: A/WSN/33.
    Natural varianti56 – 572YN → HK in strain: A/NWS/33.
    Natural varianti57 – 571N → K in strain: A/WSN/33.
    Natural varianti130 – 1301N → R in strain: A/WSN/33.
    Natural varianti130 – 1301N → Y in strain: A/NWS/33.
    Natural varianti133 – 1331V → F in strain: A/WSN/33.
    Natural varianti133 – 1331V → S in strain: A/NWS/33.
    Natural varianti184 – 1841N → D in strain: A/WSN/33.
    Natural varianti206 – 2061K → N in strain: A/WSN/33.
    Natural varianti232 – 2321N → D in strain: A/WSN/33 and A/NWS/33.
    Natural varianti297 – 2971Q → K in strain: A/WSN/33.
    Natural varianti316 – 3161P → T in strain: A/WSN/33 and A/NWS/33.
    Natural varianti336 – 3361R → K in strain: A/WSN/33.
    Natural varianti373 – 3731V → M in strain: A/WSN/33.
    Natural varianti414 – 4141R → L in strain: A/WSN/33.
    Natural varianti414 – 4141R → Q in strain: A/NWS/33.
    Natural varianti418 – 4192ET → DA in strain: A/WSN/33.
    Natural varianti434 – 4341S → G in strain: A/WSN/33.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02177 Genomic RNA. Translation: AAA43397.1. Sequence problems.
    L25815 mRNA. Translation: AAA91326.1.
    L25816 mRNA. Translation: AAA91327.1.
    L25817 mRNA. Translation: AAA91328.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02177 Genomic RNA. Translation: AAA43397.1 . Sequence problems.
    L25815 mRNA. Translation: AAA91326.1 .
    L25816 mRNA. Translation: AAA91327.1 .
    L25817 mRNA. Translation: AAA91328.1 .

    3D structure databases

    ProteinModelPortali P03470.
    SMRi P03470. Positions 67-451.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    ChEMBLi CHEMBL1287610.

    Protein family/group databases

    CAZyi GH34. Glycoside Hydrolase Family 34.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    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. "Complete nucleotide sequence of the neuraminidase gene of human influenza virus A/WSN/33."
      Hiti A.L., Nayak D.P.
      J. Virol. 41:730-734(1982) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: A/WSN/33.
    2. "Changes in the neuraminidase of neurovirulent influenza virus strains."
      Ward A.C.
      Virus Genes 10:253-260(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: A/NWS/33, A/WS/33 and A/WSN/33.
    3. "Analysis of the transmembrane domain of influenza virus neuraminidase, a type II transmembrane glycoprotein, for apical sorting and raft association."
      Barman S., Nayak D.P.
      J. Virol. 74:6538-6545(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    4. "Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication."
      Suzuki T., Takahashi T., Guo C.T., Hidari K.I., Miyamoto D., Goto H., Kawaoka Y., Suzuki Y.
      J. Virol. 79:11705-11715(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
      Strain: A/WSN/33.
    5. "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.
    6. "Neuraminidase inhibitors for influenza."
      Moscona A.
      N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    7. "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_I33A0
    AccessioniPrimary (citable) accession number: P03470
    Secondary accession number(s): Q67215, Q67216, Q67217
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: December 20, 2005
    Last modified: October 1, 2014
    This is version 105 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

    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