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P05803

- NRAM_I84A1

UniProt

P05803 - NRAM_I84A1

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Whale/Maine/1/1984 H13N9)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 112 (01 Oct 2014)
      Sequence version 1 (01 Nov 1988)
      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.

    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 sitei119 – 1191SubstrateBy similarity
    Active sitei152 – 1521Proton donor/acceptorBy similarity
    Binding sitei153 – 1531SubstrateBy similarity
    Binding sitei294 – 2941SubstrateBy similarity
    Metal bindingi295 – 2951Calcium; via carbonyl oxygen1 Publication
    Metal bindingi299 – 2991Calcium; via carbonyl oxygen1 Publication
    Metal bindingi326 – 3261Calcium1 Publication
    Metal bindingi348 – 3481Calcium; via carbonyl oxygen1 Publication
    Binding sitei372 – 3721SubstrateBy 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/Whale/Maine/1/1984 H13N9)
    Taxonomic identifieri11484 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Cetacea (whales) [TaxID: 9721]

    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 – 470470NeuraminidasePRO_0000078725Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi42 – 421N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi52 – 521N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi63 – 631N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi66 – 661N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi87 – 871N-linked (GlcNAc...); by host2 Publications
    Disulfide bondi93 ↔ 4191 Publication
    Disulfide bondi125 ↔ 1301 Publication
    Glycosylationi147 – 1471N-linked (GlcNAc...); by host1 Publication
    Disulfide bondi177 ↔ 1951 Publication
    Disulfide bondi185 ↔ 2321 Publication
    Glycosylationi202 – 2021N-linked (GlcNAc...) (high mannose); by host1 Publication
    Disulfide bondi234 ↔ 2391 Publication
    Disulfide bondi280 ↔ 2931 Publication
    Disulfide bondi282 ↔ 2911 Publication
    Disulfide bondi320 ↔ 3381 Publication
    Disulfide bondi423 ↔ 4491 Publication

    Post-translational modificationi

    N-glycosylated.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.2 Publications

    Protein-protein interaction databases

    MINTiMINT-1511103.

    Structurei

    Secondary structure

    1
    470
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi96 – 1049
    Helixi106 – 1105
    Beta strandi122 – 1265
    Beta strandi129 – 1357
    Beta strandi138 – 1436
    Helixi144 – 1463
    Turni147 – 1504
    Beta strandi158 – 1636
    Turni170 – 1723
    Beta strandi174 – 18613
    Beta strandi191 – 1988
    Beta strandi204 – 21815
    Beta strandi220 – 2234
    Beta strandi229 – 2313
    Beta strandi238 – 2469
    Beta strandi248 – 2503
    Beta strandi252 – 2609
    Beta strandi263 – 2697
    Beta strandi281 – 2855
    Beta strandi288 – 2925
    Beta strandi296 – 2983
    Beta strandi303 – 3086
    Turni309 – 3124
    Beta strandi313 – 3186
    Beta strandi326 – 3283
    Beta strandi338 – 3403
    Beta strandi354 – 3574
    Helixi358 – 3603
    Beta strandi362 – 3654
    Beta strandi369 – 37911
    Turni381 – 3855
    Beta strandi392 – 40312
    Beta strandi407 – 4104
    Beta strandi415 – 4206
    Beta strandi423 – 4319
    Turni432 – 4343
    Beta strandi437 – 4393
    Beta strandi441 – 45313
    Helixi466 – 4694

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1NCDX-ray2.90N83-470[»]
    1NMAX-ray3.00N83-470[»]
    1NMBX-ray2.20N1-470[»]
    2B8HX-ray2.20A/B/C/D83-470[»]
    ProteinModelPortaliP05803.
    SMRiP05803. Positions 83-470.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05803.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 66IntravirionSequence Analysis
    Topological domaini36 – 470435Virion 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 – 8954Hypervariable stalk regionAdd
    BLAST
    Regioni90 – 470381Head of neuraminidaseAdd
    BLAST
    Regioni278 – 2792Substrate bindingBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi345 – 3484Poly-Asn

    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.

    P05803-1 [UniParc]FASTAAdd to Basket

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    MNPNQKILCT SATALVIGTI AVLIGIVNLG LNIGLHLKPS CNCSRSQPEA    50
    TNASQTIINN YYNETNITQI SNTNIQVEER ASREFNNLTK GLCTINSWHI 100
    YGKDNAVRIG EDSDVLVTRE PYVSCDPDEC RFYALSQGTT IRGKHSNGTI 150
    HDRSQYRDLI SWPLSSPPTV YNSRVECIGW SSTSCHDGRA RMSICISGPN 200
    NNASAVIWYN RRPVTEINTW ARNILRTQES ECVCQNGVCP VVFTDGSATG 250
    PAETRIYYFK EGKILKWEPL TGTAKHIEEC SCYGEQAGVT CTCRDNWQGS 300
    NRPVIQIDPV AMTHTSQYIC SPVLTDNPRP NDPTVGKCND PYPGNNNNGV 350
    KGFSYLDGGN TWLGRTISIA SRSGYEMLKV PNALTDDRSK PTQGQTIVLN 400
    TDWSGYSGSF MDYWAEGECY RACFYVELIR GRPKEDKVWW TSNSIVSMCS 450
    STEFLGQWNW PDGAKIEYFL 470
    Length:470
    Mass (Da):52,394
    Last modified:November 1, 1988 - v1
    Checksum:iF2054DD47BBAB996
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M17812 Genomic RNA. Translation: AAA43575.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M17812 Genomic RNA. Translation: AAA43575.1 .

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1NCD X-ray 2.90 N 83-470 [» ]
    1NMA X-ray 3.00 N 83-470 [» ]
    1NMB X-ray 2.20 N 1-470 [» ]
    2B8H X-ray 2.20 A/B/C/D 83-470 [» ]
    ProteinModelPortali P05803.
    SMRi P05803. Positions 83-470.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    MINTi MINT-1511103.

    Protein family/group databases

    CAZyi GH34. Glycoside Hydrolase Family 34.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P05803.
    PROi P05803.

    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. "Distribution of sequence differences in influenza N9 neuraminidase of tern and whale viruses and crystallization of the whale neuraminidase complexed with antibodies."
      Air G.M., Webster R.G., Colman P.M., Laver W.G.
      Virology 160:346-354(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "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.
    3. "Neuraminidase inhibitors for influenza."
      Moscona A.
      N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    4. "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.
    5. "The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody."
      Malby R.L., Tulip W.R., Harley V.R., McKimm-Breschkin J.L., Laver W.G., Webster R.G., Colman P.M.
      Structure 2:733-746(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH CALCIUM; SUBSTRATE ANALOG AND THE NC10 ANTIBODY, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-87 AND ASN-147.
    6. "N9 neuraminidase complexes with antibodies NC41 and NC10: empirical free energy calculations capture specificity trends observed with mutant binding data."
      Tulip W.R., Harley V.R., Webster R.G., Novotny J.
      Biochemistry 33:7986-7997(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 83-470 IN COMPLEX WITH ANTIBODIES NC41 AND NC10, GLYCOSYLATION AT ASN-87 AND ASN-202.

    Entry informationi

    Entry nameiNRAM_I84A1
    AccessioniPrimary (citable) accession number: P05803
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1988
    Last sequence update: November 1, 1988
    Last modified: October 1, 2014
    This is version 112 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 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