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P03478

- NRAM_I72A5

UniProt

P03478 - NRAM_I72A5

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Shearwater/Australia/1972 H6N5)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi
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    • History
      Entry version 101 (01 Oct 2014)
      Sequence version 2 (01 Feb 1991)
      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 sitei110 – 1101SubstrateBy similarity
    Active sitei143 – 1431Proton donor/acceptorBy similarity
    Binding sitei144 – 1441SubstrateBy similarity
    Binding sitei285 – 2851SubstrateBy similarity
    Metal bindingi286 – 2861Calcium; via carbonyl oxygenBy similarity
    Metal bindingi290 – 2901Calcium; via carbonyl oxygenBy similarity
    Metal bindingi316 – 3161CalciumBy similarity
    Binding sitei365 – 3651SubstrateBy similarity
    Active sitei399 – 3991NucleophileBy 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/Shearwater/Australia/1972 H6N5)
    Taxonomic identifieri383604 [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 – 468468NeuraminidasePRO_0000078716Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi46 – 461N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi52 – 521N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi65 – 651N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi78 – 781N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi84 ↔ 414By similarity
    Disulfide bondi116 ↔ 121By similarity
    Glycosylationi138 – 1381N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi176 ↔ 223By similarity
    Disulfide bondi225 ↔ 230By similarity
    Disulfide bondi271 ↔ 284By similarity
    Disulfide bondi273 ↔ 282By similarity
    Disulfide bondi310 ↔ 329By similarity
    Glycosylationi395 – 3951N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi418 ↔ 444By similarity

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP03478.
    SMRiP03478. Positions 76-465.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66IntravirionSequence Analysis

    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 – 8247Hypervariable stalk regionAdd
    BLAST
    Regioni83 – 468386Head of neuraminidaseAdd
    BLAST
    Regioni269 – 2702Substrate bindingBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi437 – 4404Poly-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.

    P03478-1 [UniParc]FASTAAdd to Basket

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    MNPNQKIITI GSASLGLVIF NILLHVASIT LGIISVTKDN KVHICNTTEV    50
    YNETVRVETV VIPVNNTIYL NHEPEFLNNT EPLCDVSGFA IVSKDNGIRI 100
    GSRGHIFVIR EPFVSCGPSE CRTFFLTQGA LLNDKHSNNT VKDRSPYRAL 150
    MSVPLGSSPN AYQAKFESVG WSATACHDGK KWMAIGVSGA DDDAYAVIHY 200
    GGVPTDVIRS WRKQILRTQE SSCVCIKGEC YWVMTDGPAN NQASYKIFKS 250
    QKGMVVDEKE ISFQGGHIEE CSCYPNMGKV ECVCRDNWNG MNRPILIFDE 300
    KLEYEVGYLC AGIPTDTPRV QDSSFTGSCT NAVGRSGTNN YGVKGFGFRQ 350
    GNSVWAGRTI SVSSRSGFEV LLIEDGWIRP SKTISKKVEV LNNKNWSGYS 400
    GAFTIPTAMT SKNCIVPCFW LEMIRGKPEE RTSIWTSSSS TVFCGVSSEV 450
    PGWSWDDGAI LPFDIDKM 468
    Length:468
    Mass (Da):51,590
    Last modified:February 1, 1991 - v2
    Checksum:i58A235445B2D3F1F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti26 – 261V → G in CAA24278. (PubMed:6896994)Curated
    Sequence conflicti31 – 333LGI → WGT in CAA24278. (PubMed:6896994)Curated
    Sequence conflicti50 – 501V → A in CAA24278. (PubMed:6896994)Curated
    Sequence conflicti55 – 595VRVET → ARAEK in CAA24278. (PubMed:6896994)Curated
    Sequence conflicti69 – 702YL → HS in CAA24278. (PubMed:6896994)Curated
    Sequence conflicti84 – 841C → R in CAA24278. (PubMed:6896994)Curated
    Sequence conflicti94 – 10714KDNGI…RGHIF → NGHGTRTGQEGTHS in CAA24278. (PubMed:6896994)CuratedAdd
    BLAST
    Sequence conflicti115 – 1151S → A in BAF36387. 1 PublicationCurated
    Sequence conflicti335 – 3351R → G in BAF36387. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M24740 Genomic RNA. Translation: AAA43672.1.
    AB278601 Genomic RNA. Translation: BAF36387.1.
    V01094 Unassigned RNA. Translation: CAA24278.1.
    PIRiA00890. NMIVN5.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M24740 Genomic RNA. Translation: AAA43672.1 .
    AB278601 Genomic RNA. Translation: BAF36387.1 .
    V01094 Unassigned RNA. Translation: CAA24278.1 .
    PIRi A00890. NMIVN5.

    3D structure databases

    ProteinModelPortali P03478.
    SMRi P03478. Positions 76-465.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    CAZyi GH34. Glycoside Hydrolase Family 34.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    PROi P03478.

    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. "Molecular cloning and analysis of the N5 neuraminidase subtype from an avian influenza virus."
      Harley V.R., Ward C.W., Hudson P.J.
      Virology 169:239-243(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "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 (NOV-2006) to the EMBL/GenBank/DDBJ databases
      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 1-107.
    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_I72A5
    AccessioniPrimary (citable) accession number: P03478
    Secondary accession number(s): A0A9J2, Q84104
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: February 1, 1991
    Last modified: October 1, 2014
    This is version 101 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