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P06820

- NRAM_I67A0

UniProt

P06820 - NRAM_I67A0

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Tokyo/3/1967 H2N2)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 113 (01 Oct 2014)
      Sequence version 2 (01 Oct 1996)
      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.3 Publications

    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 sitei118 – 1181Substrate
    Active sitei151 – 1511Proton donor/acceptorBy similarity
    Binding sitei152 – 1521Substrate
    Binding sitei292 – 2921Substrate
    Metal bindingi293 – 2931Calcium; via carbonyl oxygen3 Publications
    Metal bindingi297 – 2971Calcium; via carbonyl oxygen3 Publications
    Metal bindingi324 – 3241Calcium3 Publications
    Metal bindingi345 – 3451Calcium; via carbonyl oxygen3 Publications
    Metal bindingi346 – 3461Calcium; via carbonyl oxygen3 Publications
    Metal bindingi347 – 3471Calcium; via carbonyl oxygen3 Publications
    Binding sitei371 – 3711Substrate
    Active sitei406 – 4061NucleophileBy 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

    Enzyme and pathway databases

    SABIO-RKP06820.

    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/Tokyo/3/1967 H2N2)
    Taxonomic identifieri380960 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Homo sapiens (Human) [TaxID: 9606]

    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. 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 – 469469NeuraminidasePRO_0000078720Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi61 – 611N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi69 – 691N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi70 – 701N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi86 – 861N-linked (GlcNAc...); by host3 Publications
    Disulfide bondi92 ↔ 417
    Disulfide bondi124 ↔ 129
    Glycosylationi146 – 1461N-linked (GlcNAc...); by host3 Publications
    Disulfide bondi175 ↔ 193
    Disulfide bondi183 ↔ 230
    Glycosylationi200 – 2001N-linked (GlcNAc...); by host3 Publications
    Disulfide bondi232 ↔ 237
    Glycosylationi234 – 2341N-linked (GlcNAc...); by host2 Publications
    Disulfide bondi278 ↔ 291
    Disulfide bondi280 ↔ 289
    Disulfide bondi318 ↔ 337
    Disulfide bondi421 ↔ 447

    Post-translational modificationi

    N-glycosylated.3 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.3 Publications

    Structurei

    Secondary structure

    1
    469
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi96 – 1027
    Helixi105 – 1084
    Turni109 – 1113
    Beta strandi121 – 1244
    Beta strandi129 – 1324
    Beta strandi137 – 1393
    Turni144 – 1496
    Beta strandi157 – 1626
    Beta strandi172 – 1765
    Beta strandi178 – 1847
    Beta strandi186 – 19611
    Beta strandi198 – 20710
    Beta strandi210 – 2167
    Beta strandi218 – 2214
    Beta strandi227 – 2293
    Beta strandi231 – 2333
    Beta strandi236 – 2449
    Beta strandi246 – 2483
    Beta strandi250 – 26718
    Beta strandi276 – 2816
    Beta strandi284 – 2929
    Beta strandi294 – 2963
    Beta strandi301 – 3055
    Turni307 – 3093
    Beta strandi312 – 3165
    Beta strandi319 – 3213
    Beta strandi324 – 3263
    Beta strandi330 – 3323
    Beta strandi337 – 3393
    Beta strandi353 – 3564
    Beta strandi359 – 3668
    Beta strandi368 – 3714
    Beta strandi374 – 3818
    Turni382 – 3843
    Beta strandi385 – 3873
    Beta strandi390 – 3934
    Beta strandi407 – 4137
    Beta strandi415 – 42915
    Turni430 – 4323
    Beta strandi435 – 4373
    Beta strandi439 – 45113
    Turni464 – 4663

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1INGX-ray2.40A/B82-469[»]
    1INHX-ray2.40A/B82-469[»]
    1INWX-ray2.40A82-469[»]
    1INXX-ray2.40A82-469[»]
    1IVCX-ray2.40A/B82-469[»]
    1IVDX-ray1.90A/B82-469[»]
    1IVEX-ray2.40A/B82-469[»]
    1IVFX-ray2.40A/B82-469[»]
    1IVGX-ray1.90A/B82-469[»]
    1NN2X-ray2.20A82-469[»]
    2BATX-ray2.00A82-469[»]
    ProteinModelPortaliP06820.
    SMRiP06820. Positions 82-469.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP06820.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66IntravirionSequence Analysis
    Topological domaini36 – 469434Virion 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 – 9055Hypervariable stalk regionAdd
    BLAST
    Regioni91 – 469379Head of neuraminidaseAdd
    BLAST
    Regioni276 – 2772Substrate bindingBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi179 – 1824Poly-Ser

    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.

    P06820-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNPNQKIITI GSVSLTIATV CFLMQIAILV TTVTLHFKQH ECDSPASNQV    50
    MPCEPIIIER NITEIVYLNN TTIEKEICPK VVEYRNWSKP QCQITGFAPF 100
    SKDNSIRLSA GGDIWVTREP YVSCDPVKCY QFALGQGTTL DNKHSNDTVH 150
    DRIPHRTLLM NELGVPFHLG TRQVCIAWSS SSCHDGKAWL HVCITGDDKN 200
    ATASFIYDGR LVDSIGSWSQ NILRTQESEC VCINGTCTVV MTDGSASGRA 250
    DTRILFIEEG KIVHISPLAG SAQHVEECSC YPRYPGVRCI CRDNWKGSNR 300
    PVVDINMEDY SIDSSYVCSG LVGDTPRNDD RSSNSNCRNP NNERGTQGVK 350
    GWAFDNGNDL WMGRTISKDL RSGYETFKVI GGWSTPNSKS QINRQVIVDS 400
    DNRSGYSGIF SVEGKSCINR CFYVELIRGR KQETRVWWTS NSIVVFCGTS 450
    GTYGTGSWPD GANINFMPI 469
    Length:469
    Mass (Da):52,131
    Last modified:October 1, 1996 - v2
    Checksum:iDF9F74BFFA3FEBC9
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti41 – 411E → D in AAO46245. (PubMed:15380362)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01393 Genomic RNA. Translation: AAB05621.1.
    AY209929 Genomic RNA. Translation: AAO46245.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K01393 Genomic RNA. Translation: AAB05621.1 .
    AY209929 Genomic RNA. Translation: AAO46245.1 .

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1ING X-ray 2.40 A/B 82-469 [» ]
    1INH X-ray 2.40 A/B 82-469 [» ]
    1INW X-ray 2.40 A 82-469 [» ]
    1INX X-ray 2.40 A 82-469 [» ]
    1IVC X-ray 2.40 A/B 82-469 [» ]
    1IVD X-ray 1.90 A/B 82-469 [» ]
    1IVE X-ray 2.40 A/B 82-469 [» ]
    1IVF X-ray 2.40 A/B 82-469 [» ]
    1IVG X-ray 1.90 A/B 82-469 [» ]
    1NN2 X-ray 2.20 A 82-469 [» ]
    2BAT X-ray 2.00 A 82-469 [» ]
    ProteinModelPortali P06820.
    SMRi P06820. Positions 82-469.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P06820.

    Protein family/group databases

    CAZyi GH34. Glycoside Hydrolase Family 34.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Enzyme and pathway databases

    SABIO-RK P06820.

    Miscellaneous databases

    EvolutionaryTracei P06820.
    PROi P06820.

    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. "Sequence of the neuraminidase gene of influenza virus A/Tokyo/3/67 and previously uncharacterized monoclonal variants."
      Lentz M.R., Air G.M., Laver W.G., Webster R.G.
      Virology 135:257-265(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. Air G.M.
      Submitted (JUL-1996) to UniProtKB
      Cited for: SEQUENCE REVISION TO 420.
    3. "Genetic analysis of human H2N2 and early H3N2 influenza viruses, 1957-1972: evidence for genetic divergence and multiple reassortment events."
      Lindstrom S.E., Cox N.J., Klimov A.
      Virology 328:101-119(2004) [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.
    7. "Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2-A resolution."
      Varghese J.N., Colman P.M.
      J. Mol. Biol. 221:473-486(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 82-469 IN COMPLEX WITH CALCIUM, GLYCOSYLATION AT ASN-86; ASN-146 AND ASN-200, COFACTOR, SUBUNIT, DISULFIDE BOND.
    8. "A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies."
      White C.L., Janakiraman M.N., Laver W.G., Philippon C., Vasella A., Air G.M., Luo M.
      J. Mol. Biol. 245:623-634(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 82-469 IN COMPLEX WITH SUBSTRATE ANALOG AND CALCIUM, GLYCOSYLATION AT ASN-86; ASN-146; ASN-200 AND ASN-234, COFACTOR, SUBUNIT, DISULFIDE BOND.
    9. "Structures of aromatic inhibitors of influenza virus neuraminidase."
      Jedrzejas M.J., Singh S., Brouillette W.J., Laver W.G., Air G.M., Luo M.
      Biochemistry 34:3144-3151(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 82-469 IN COMPLEX WITH 2-DEOXY-2,3-DEHYDRO-N-ACETYL-NEURAMINIC ACID AND CALCIUM, DISULFIDE BONDS, GLYCOSYLATION AT ASN-86; ASN-146; ASN-200 AND ASN-234, COFACTOR.

    Entry informationi

    Entry nameiNRAM_I67A0
    AccessioniPrimary (citable) accession number: P06820
    Secondary accession number(s): Q6XUB0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 113 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

    3D-structure

    Documents

    1. Glycosyl hydrolases
      Classification of glycosyl hydrolase families and list of entries
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3