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P03475

- NRAM_I72A3

UniProt

P03475 - NRAM_I72A3

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Memphis/102/1972 H3N2)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi
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    • History
      Entry version 97 (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 sitei118 – 1181SubstrateBy similarity
    Active sitei151 – 1511Proton donor/acceptorBy similarity
    Binding sitei152 – 1521SubstrateBy similarity
    Binding sitei292 – 2921SubstrateBy similarity
    Metal bindingi293 – 2931Calcium; via carbonyl oxygenBy similarity
    Metal bindingi297 – 2971Calcium; via carbonyl oxygenBy similarity
    Metal bindingi324 – 3241CalciumBy similarity
    Binding sitei371 – 3711SubstrateBy similarity
    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

    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/Memphis/102/1972 H3N2)
    Taxonomic identifieri385640 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Cetacea (whales) [TaxID: 9721]
    Homo sapiens (Human) [TaxID: 9606]
    Phocidae (true seals) [TaxID: 9709]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000007790: 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. 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_0000078708Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi61 – 611N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi70 – 701N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi86 – 861N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi92 ↔ 417By similarity
    Disulfide bondi124 ↔ 129By similarity
    Glycosylationi146 – 1461N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi175 ↔ 193By similarity
    Disulfide bondi183 ↔ 230By similarity
    Glycosylationi200 – 2001N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi232 ↔ 237By similarity
    Glycosylationi234 – 2341N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi278 ↔ 291By similarity
    Disulfide bondi280 ↔ 289By similarity
    Disulfide bondi318 ↔ 337By similarity
    Glycosylationi402 – 4021N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi421 ↔ 447By similarity

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP03475.
    SMRiP03475. Positions 82-469.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 99IntravirionSequence Analysis
    Topological domaini31 – 469439Virion surfaceSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei10 – 3021Helical; 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
    Regioni39 – 9052Hypervariable stalk regionBy similarityAdd
    BLAST
    Regioni91 – 467377Head of neuraminidaseBy similarityAdd
    BLAST
    Regioni276 – 2772Substrate 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.

    P03475-1 [UniParc]FASTAAdd to Basket

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    MNPNQKIITI GSVSLTIATI CFLMQIAILV TTVTLHFKQY ECDSPANNQV    50
    MPCEPIIIER NITEIVYLTN TTIEKEICPK LVEYRNWSKP QCKITGFAPF 100
    SKDNSIRLSA GGDIWVTREP YVSCDPGKCY QFALGQGTTL DNKHSNDTIH 150
    DRTPHRTLLM NELGVPFHLG TRQVCIAWSS SSCHDGKAWL HVCVTGYDKN 200
    ATASFIYDGR LVDSIGSWSQ NILRTQESEC VCINGTCTVV MTDGSASGRA 250
    DTKILFIEEG KIVHISPLSG SAQHVEECSC YPRYPGVRCI CRDNWKGSNR 300
    PVVDINVKDY SIDSSYVCSG LVGDTPRNND RSSNSYCRNP NNEKGNHGVK 350
    GWAFDDGNDV WMGRTISEDS RSGYETFKVI GGWSTPNSKL QINRQVIVDS 400
    DNRSGYSGIF SVEGKSCINR CFYVELIRGR EQETRVWWTS NSIVVFCGTS 450
    GTYGTGSWPD GADINLMPI 469
    Length:469
    Mass (Da):52,146
    Last modified:March 6, 2007 - v2
    Checksum:i005D07E579580B27
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti28 – 281I → M in CAA24275. (PubMed:6896994)Curated
    Sequence conflicti46 – 461A → G in CAA24275. (PubMed:6896994)Curated
    Sequence conflicti51 – 522MP → TL in CAA24275. (PubMed:6896994)Curated
    Sequence conflicti67 – 671Y → H in CAA24275. (PubMed:6896994)Curated
    Sequence conflicti383 – 3842WS → LF in BAD16643. (PubMed:14741372)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB124659 Genomic RNA. Translation: BAD16643.1.
    CY002098 Genomic RNA. Translation: AAZ43386.1.
    V01091 Unassigned RNA. Translation: CAA24275.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB124659 Genomic RNA. Translation: BAD16643.1 .
    CY002098 Genomic RNA. Translation: AAZ43386.1 .
    V01091 Unassigned RNA. Translation: CAA24275.1 .

    3D structure databases

    ProteinModelPortali P03475.
    SMRi P03475. Positions 82-469.
    ModBasei Search...
    MobiDBi Search...

    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. "Evolutional analysis of human influenza A virus N2 neuraminidase genes based on the transition of the low-pH stability of sialidase activity."
      Suzuki T., Takahashi T., Saito T., Guo C.T., Hidari K.I.-P.J., Miyamoto D., Suzuki Y.
      FEBS Lett. 557:228-232(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    3. "Variation in the membrane-insertion and 'stalk' sequences in eight subtypes of influenza type A virus neuraminidase."
      Blok J., Air G.M.
      Biochemistry 21:4001-4007(1982) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-91.
    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.

    Entry informationi

    Entry nameiNRAM_I72A3
    AccessioniPrimary (citable) accession number: P03475
    Secondary accession number(s): Q463X2, Q75VQ3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: March 6, 2007
    Last modified: October 1, 2014
    This is version 97 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