Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P03474

- NRAM_INBLE

UniProt

P03474 - NRAM_INBLE

Protein

Neuraminidase

Gene

NA

Organism
Influenza B virus (strain B/Lee/1940)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 1 (21 Jul 1986)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 By similarity.By similarity

    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 sitei116 – 1161SubstrateBy similarity
    Active sitei149 – 1491Proton donor/acceptorBy similarity
    Binding sitei150 – 1501SubstrateBy similarity
    Binding sitei292 – 2921SubstrateBy similarity
    Metal bindingi293 – 2931Calcium; via carbonyl oxygen2 Publications
    Metal bindingi297 – 2971Calcium; via carbonyl oxygen2 Publications
    Metal bindingi324 – 3241Calcium2 Publications
    Metal bindingi346 – 3461Calcium; via carbonyl oxygen2 Publications
    Binding sitei374 – 3741SubstrateBy similarity
    Active sitei409 – 4091NucleophileBy 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

    GO - Biological processi

    1. carbohydrate metabolic process Source: InterPro

    Keywords - Molecular functioni

    Glycosidase, Hydrolase

    Keywords - Ligandi

    Calcium, Metal-binding

    Enzyme and pathway databases

    SABIO-RKP03474.

    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 B virus (strain B/Lee/1940)
    Taxonomic identifieri107412 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus B
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000008158: 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. 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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi117 – 1171E → G: Reduced substrate binding. 1 Publication
    Mutagenesisi149 – 1491D → E: Almost complete loss of enzymatic activity. 1 Publication
    Mutagenesisi150 – 1501R → K: Reduced substrate binding. 1 Publication
    Mutagenesisi223 – 2231R → K: Reduced substrate binding. 1 Publication
    Mutagenesisi275 – 2751E → D: Almost complete loss of enzymatic activity. 1 Publication
    Mutagenesisi374 – 3741R → K: 80% loss of catalytic efficiency. 1 Publication
    Mutagenesisi374 – 3741R → N: 94% loss of catalytic efficiency. 1 Publication
    Mutagenesisi409 – 4091Y → F: Complete loss of enzymatic activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 466466NeuraminidasePRO_0000078732Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi56 – 561N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi64 – 641N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi87 ↔ 420
    Disulfide bondi122 ↔ 127
    Glycosylationi144 – 1441N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi182 ↔ 229
    Disulfide bondi231 ↔ 236
    Disulfide bondi277 ↔ 291
    Disulfide bondi279 ↔ 289
    Glycosylationi284 – 2841N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi318 ↔ 337
    Disulfide bondi424 ↔ 447

    Post-translational modificationi

    N-glycosylated.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.3 Publications

    Structurei

    Secondary structure

    1
    466
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi88 – 903
    Beta strandi92 – 987
    Helixi100 – 1023
    Beta strandi106 – 1083
    Beta strandi119 – 1224
    Beta strandi127 – 1337
    Beta strandi137 – 1393
    Turni144 – 1474
    Beta strandi155 – 1606
    Turni167 – 1693
    Beta strandi171 – 1755
    Beta strandi177 – 1837
    Beta strandi185 – 19511
    Turni197 – 1993
    Beta strandi201 – 2066
    Beta strandi209 – 2157
    Beta strandi217 – 2204
    Beta strandi226 – 2283
    Beta strandi230 – 2323
    Beta strandi235 – 2417
    Beta strandi245 – 2473
    Beta strandi251 – 2577
    Beta strandi260 – 2656
    Beta strandi268 – 2703
    Beta strandi275 – 29218
    Beta strandi294 – 2963
    Beta strandi301 – 3066
    Turni307 – 3104
    Beta strandi311 – 3166
    Beta strandi324 – 3263
    Beta strandi352 – 3565
    Beta strandi361 – 3677
    Beta strandi369 – 38517
    Turni387 – 3893
    Beta strandi395 – 40612
    Beta strandi410 – 4167
    Beta strandi418 – 43215
    Beta strandi435 – 4373
    Beta strandi439 – 44810
    Beta strandi450 – 4523

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1B9SX-ray2.50A77-466[»]
    1B9TX-ray2.40A77-466[»]
    1B9VX-ray2.35A77-466[»]
    1INFX-ray2.40A77-466[»]
    1INVX-ray2.40A77-466[»]
    1IVBX-ray2.40A77-466[»]
    1VCJX-ray2.40A78-466[»]
    ProteinModelPortaliP03474.
    SMRiP03474. Positions 77-466.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03474.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66IntravirionSequence Analysis
    Topological domaini36 – 466431Virion 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
    Regioni39 – 6931Hypervariable stalk regionAdd
    BLAST
    Regioni70 – 466397Head of neuraminidaseAdd
    BLAST
    Regioni275 – 2762Substrate bindingBy 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.

    P03474-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLPSTVQTLT LLLTSGGVLL SLYVSASLSY LLYSDVLLKF SSTKTTAPTM    50
    SLECTNASNA QTVNHSATKE MTFPPPEPEW TYPRLSCQGS TFQKALLISP 100
    HRFGEIKGNS APLIIREPFV ACGPKECRHF ALTHYAAQPG GYYNGTRKDR 150
    NKLRHLVSVK LGKIPTVENS IFHMAAWSGS ACHDGREWTY IGVDGPDNDA 200
    LVKIKYGEAY TDTYHSYAHN ILRTQESACN CIGGDCYLMI TDGSASGISK 250
    CRFLKIREGR IIKEILPTGR VEHTEECTCG FASNKTIECA CRDNSYTAKR 300
    PFVKLNVETD TAEIRLMCTK TYLDTPRPDD GSIAGPCESN GDKWLGGIKG 350
    GFVHQRMASK IGRWYSRTMS KTNRMGMELY VKYDGDPWTD SDALTLSGVM 400
    VSIEEPGWYS FGFEIKDKKC DVPCIGIEMV HDGGKDTWHS AATAIYCLMG 450
    SGQLLWDTVT GVDMAL 466
    Length:466
    Mass (Da):51,442
    Last modified:July 21, 1986 - v1
    Checksum:iE6FF3E634F132263
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02095 Genomic RNA. Translation: AAA43749.1.
    PIRiA00886. NMIV4.
    RefSeqiNP_056663.1. NC_002209.1.

    Genome annotation databases

    GeneIDi956541.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02095 Genomic RNA. Translation: AAA43749.1 .
    PIRi A00886. NMIV4.
    RefSeqi NP_056663.1. NC_002209.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1B9S X-ray 2.50 A 77-466 [» ]
    1B9T X-ray 2.40 A 77-466 [» ]
    1B9V X-ray 2.35 A 77-466 [» ]
    1INF X-ray 2.40 A 77-466 [» ]
    1INV X-ray 2.40 A 77-466 [» ]
    1IVB X-ray 2.40 A 77-466 [» ]
    1VCJ X-ray 2.40 A 78-466 [» ]
    ProteinModelPortali P03474.
    SMRi P03474. Positions 77-466.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P03474.
    ChEMBLi CHEMBL3377.

    Protein family/group databases

    CAZyi GH34. Glycoside Hydrolase Family 34.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 956541.

    Enzyme and pathway databases

    SABIO-RK P03474.

    Miscellaneous databases

    EvolutionaryTracei P03474.

    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 influenza B virus."
      Shaw M.W., Lamb R.A., Erickson B.W., Briedis D.J., Choppin P.W.
      Proc. Natl. Acad. Sci. U.S.A. 79:6817-6821(1982) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "Site-directed mutagenesis of catalytic residues of influenza virus neuraminidase as an aid to drug design."
      Ghate A.A., Air G.M.
      Eur. J. Biochem. 258:320-331(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF GLU-117; ASP-149; ARG-150; ARG-223; GLU-275; ARG-374 AND TYR-409.
    3. "Neuraminidase inhibitors for influenza."
      Moscona A.
      N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    4. "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 (2.40 ANGSTROMS) OF 77-466 IN COMPLEX WITH SYNTHETIC INHIBITOR AND CALCIUM, SUBUNIT, COFACTOR, GLYCOSYLATION AT ASN-284.
    5. "Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site."
      Finley J.B., Atigadda V.R., Duarte F., Zhao J.J., Brouillette W.J., Air G.M., Luo M.
      J. Mol. Biol. 293:1107-1119(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-466 IN COMPLEX WITH SYNTHETIC INHIBITOR AND CALCIUM, SUBUNIT, COFACTOR.
    6. "A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase."
      Lommer B.S., Ali S.M., Bajpai S.N., Brouillette W.J., Air G.M., Luo M.
      Acta Crystallogr. D 60:1017-1023(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 78-466 IN COMPLEX WITH SYNTHETIC INHIBITOR, SUBUNIT, COFACTOR.

    Entry informationi

    Entry nameiNRAM_INBLE
    AccessioniPrimary (citable) accession number: P03474
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 21, 1986
    Last modified: October 1, 2014
    This is version 107 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    The influenza B 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, Complete proteome, Reference proteome

    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