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P03476

- NRAM_I71A2

UniProt

P03476 - NRAM_I71A2

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Turkey/Oregon/1971 H7N3)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi
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    • History
      Entry version 90 (01 Oct 2014)
      Sequence version 2 (20 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 sitei293 – 2931SubstrateBy similarity
    Metal bindingi294 – 2941Calcium; via carbonyl oxygenBy similarity
    Metal bindingi298 – 2981Calcium; via carbonyl oxygenBy similarity
    Metal bindingi324 – 3241CalciumBy similarity
    Binding sitei370 – 3701SubstrateBy similarity
    Active sitei405 – 4051NucleophileBy 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/Turkey/Oregon/1971 H7N3)
    Taxonomic identifieri385636 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]

    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_0000078719Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi57 – 571N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi66 – 661N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi72 – 721N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi92 ↔ 416By similarity
    Disulfide bondi124 ↔ 129By similarity
    Glycosylationi146 – 1461N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi176 ↔ 194By similarity
    Disulfide bondi184 ↔ 231By similarity
    Disulfide bondi233 ↔ 238By similarity
    Disulfide bondi280 ↔ 292By similarity
    Disulfide bondi282 ↔ 290By similarity
    Glycosylationi308 – 3081N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi318 ↔ 336By similarity
    Disulfide bondi420 ↔ 447By similarity

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP03476.
    SMRiP03476. Positions 88-469.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66IntravirionSequence Analysis
    Topological domaini30 – 469440Virion surfaceSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei7 – 2923Helical; 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 – 469379Head of neuraminidaseBy similarityAdd
    BLAST
    Regioni278 – 2792Substrate 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.

    P03476-1 [UniParc]FASTAAdd to Basket

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    MNPNQKIITI GVVNTTLSTI ALLIGVGNLV FNTVIHEKIG NHQTVIHPTI    50
    TTPAVPNCSD TIITYNNTVI NNITTTIITE AERLFKPPLP LCPFRGFFPF 100
    HKDNAIRLGE NKDVIVTREP YVSCDNDNCW SFALAQGALL GTKHSNGTIK 150
    DRTPYRSLIR FPIGTAPVLG NYKEICIAWS SSSCFDGKEW MHVCMTGNDN 200
    DASAQIIYAG RMTDSIKSWR KDILRTQESE CQCIGGTCVV AVTDGPAANS 250
    ADHRVYWIRE GRIVKYENVP KTKIQHLEEC SCYVDIDVYC ICRDNWKGSN 300
    RPWMRINNET ILETGYVCSK FHSDTPRPAD PSTVSCDSPS NINGGPGVKG 350
    FGFKAGNDVW LGRTVSTSGR SGFEIIKVTD GWINSPNHAK SVTQTLVSNN 400
    DWSGYSGSFI VKTKGCFQPC FYVELIRGRP NKNDDVSWTS NSIVTFCGLD 450
    NEPGSGNWPD GSNIGFMPK 469
    Length:469
    Mass (Da):51,790
    Last modified:March 20, 2007 - v2
    Checksum:i1758078B2ABE0F65
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti94 – 941F → S in CAA24276. (PubMed:6896994)Curated
    Sequence conflicti94 – 941F → S in AAA43361. (PubMed:6927853)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB276110 Genomic RNA. Translation: BAF34372.1.
    V01092 Genomic RNA. Translation: CAA24276.1.
    K01011 Genomic RNA. Translation: AAA43361.1.
    DQ870890 Genomic RNA. Translation: ABH04381.1.
    DQ870896 Genomic RNA. Translation: ABH04387.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB276110 Genomic RNA. Translation: BAF34372.1 .
    V01092 Genomic RNA. Translation: CAA24276.1 .
    K01011 Genomic RNA. Translation: AAA43361.1 .
    DQ870890 Genomic RNA. Translation: ABH04381.1 .
    DQ870896 Genomic RNA. Translation: ABH04387.1 .

    3D structure databases

    ProteinModelPortali P03476.
    SMRi P03476. Positions 88-469.
    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. "Establishment of gene library of all haemagglutinin (HA) and neuraminidase (NA) subtypes for the control of influenza A virus infection."
      Kida H., Sakoda Y.
      Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "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 1-94.
    3. "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 1-94.
    4. "Amelioration of influenza virus pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene."
      Cauthen A.N., Swayne D.E., Sekellick M.J., Marcus P.I., Suarez D.L.
      J. Virol. 81:1838-1847(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    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_I71A2
    AccessioniPrimary (citable) accession number: P03476
    Secondary accession number(s): Q05JI0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: March 20, 2007
    Last modified: October 1, 2014
    This is version 90 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.

    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