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P03472

- NRAM_I75A5

UniProt

P03472 - NRAM_I75A5

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (21 Jul 1986)
      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.1 Publication

    Cofactori

    Binds 1 calcium ion per subunit.4 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. Inhibited by difluorosialic acid derivatives. Resistance to neuraminidase inhibitors is quite rare.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei119 – 1191Substrate
    Active sitei152 – 1521Proton donor/acceptor
    Binding sitei153 – 1531Substrate
    Binding sitei294 – 2941Substrate
    Metal bindingi295 – 2951Calcium; via carbonyl oxygen4 Publications
    Metal bindingi299 – 2991Calcium; via carbonyl oxygen4 Publications
    Metal bindingi326 – 3261Calcium4 Publications
    Metal bindingi348 – 3481Calcium; via carbonyl oxygen4 Publications
    Binding sitei372 – 3721Substrate
    Active sitei406 – 4061Nucleophile

    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/Tern/Australia/G70C/1975 H11N9)
    Taxonomic identifieri384509 [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 – 470470NeuraminidasePRO_0000078721Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi63 – 631N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi66 – 661N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi87 – 871N-linked (GlcNAc...); by host3 Publications
    Disulfide bondi93 ↔ 419
    Disulfide bondi125 ↔ 130
    Glycosylationi147 – 1471N-linked (GlcNAc...); by host3 Publications
    Disulfide bondi177 ↔ 195
    Disulfide bondi185 ↔ 232
    Glycosylationi202 – 2021N-linked (GlcNAc...); by host3 Publications
    Disulfide bondi234 ↔ 239
    Disulfide bondi280 ↔ 293
    Disulfide bondi282 ↔ 291
    Disulfide bondi320 ↔ 338
    Disulfide bondi423 ↔ 449

    Post-translational modificationi

    N-glycosylated.3 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Interactioni

    Subunit structurei

    Homotetramer.4 Publications

    Structurei

    Secondary structure

    1
    470
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi96 – 1038
    Helixi106 – 1105
    Beta strandi115 – 12612
    Beta strandi129 – 14315
    Helixi144 – 1463
    Turni147 – 1504
    Beta strandi158 – 1636
    Turni170 – 1723
    Beta strandi174 – 18613
    Beta strandi188 – 19811
    Beta strandi200 – 2023
    Beta strandi204 – 2096
    Beta strandi212 – 2187
    Beta strandi220 – 2234
    Beta strandi225 – 2273
    Beta strandi229 – 2313
    Beta strandi238 – 2469
    Beta strandi248 – 2503
    Beta strandi252 – 2609
    Beta strandi263 – 2697
    Beta strandi278 – 2858
    Beta strandi288 – 2947
    Beta strandi296 – 2983
    Beta strandi303 – 3086
    Turni309 – 3124
    Beta strandi313 – 3186
    Beta strandi321 – 3233
    Beta strandi326 – 3283
    Beta strandi338 – 3403
    Helixi358 – 3603
    Beta strandi362 – 3654
    Beta strandi369 – 37911
    Turni381 – 3855
    Beta strandi392 – 40312
    Beta strandi407 – 4104
    Beta strandi416 – 4205
    Beta strandi423 – 4319
    Turni432 – 4343
    Beta strandi441 – 45313
    Helixi466 – 4694

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1A14X-ray2.50N83-470[»]
    1BJIX-ray2.00A83-470[»]
    1F8BX-ray1.80A83-470[»]
    1F8CX-ray1.70A83-470[»]
    1F8DX-ray1.40A83-470[»]
    1F8EX-ray1.40A83-470[»]
    1INYX-ray2.40A83-470[»]
    1L7FX-ray1.80A83-470[»]
    1L7GX-ray1.85A83-470[»]
    1L7HX-ray1.85A83-470[»]
    1MWEX-ray1.70A83-470[»]
    1NCAX-ray2.50N82-470[»]
    1NCBX-ray2.50N82-470[»]
    1NCCX-ray2.50N82-470[»]
    1NMCX-ray2.50A/N83-470[»]
    1NNAX-ray2.50A84-470[»]
    1NNBX-ray2.80A84-470[»]
    1NNCX-ray1.80A83-470[»]
    1XOEX-ray2.20A84-470[»]
    1XOGX-ray2.80A84-470[»]
    2C4AX-ray2.15A83-470[»]
    2C4LX-ray2.15A83-470[»]
    2QWAX-ray1.70A83-470[»]
    2QWBX-ray2.00A83-470[»]
    2QWCX-ray1.60A83-470[»]
    2QWDX-ray2.00A83-470[»]
    2QWEX-ray2.00A83-470[»]
    2QWFX-ray1.90A83-470[»]
    2QWGX-ray1.80A83-470[»]
    2QWHX-ray1.80A83-470[»]
    2QWIX-ray2.00A83-470[»]
    2QWJX-ray2.00A83-470[»]
    2QWKX-ray1.80A83-470[»]
    3NN9X-ray2.30A83-470[»]
    3W09X-ray2.00A83-470[»]
    4DGRX-ray1.55A82-470[»]
    4NN9X-ray2.30A83-470[»]
    5NN9X-ray2.30A83-470[»]
    6NN9X-ray2.30A83-470[»]
    7NN9X-ray2.00A83-470[»]
    ProteinModelPortaliP03472.
    SMRiP03472. Positions 82-470.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03472.

    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 – 9156Hypervariable stalk regionAdd
    BLAST
    Regioni92 – 470379Head of neuraminidaseAdd
    BLAST
    Regioni278 – 2792Substrate binding

    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.

    P03472-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNPNQKILCT SATALVIGTI AVLIGITNLG LNIGLHLKPS CNCSHSQPEA    50
    TNASQTIINN YYNDTNITQI SNTNIQVEER AIRDFNNLTK GLCTINSWHI 100
    YGKDNAVRIG EDSDVLVTRE PYVSCDPDEC RFYALSQGTT IRGKHSNGTI 150
    HDRSQYRALI SWPLSSPPTV YNSRVECIGW SSTSCHDGKT RMSICISGPN 200
    NNASAVIWYN RRPVTEINTW ARNILRTQES ECVCHNGVCP VVFTDGSATG 250
    PAETRIYYFK EGKILKWEPL AGTAKHIEEC SCYGERAEIT CTCRDNWQGS 300
    NRPVIRIDPV AMTHTSQYIC SPVLTDNPRP NDPTVGKCND PYPGNNNNGV 350
    KGFSYLDGVN TWLGRTISIA SRSGYEMLKV PNALTDDKSK PTQGQTIVLN 400
    TDWSGYSGSF MDYWAEGECY RACFYVELIR GRPKEDKVWW TSNSIVSMCS 450
    STEFLGQWDW PDGAKIEYFL 470
    Length:470
    Mass (Da):52,469
    Last modified:July 21, 1986 - v1
    Checksum:iF114226CF93E1370
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti377 – 3771M → I in AAA43574. (PubMed:3660585)Curated
    Sequence conflicti387 – 3882DK → ER in AAA43574. (PubMed:3660585)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M11445 Genomic RNA. Translation: AAA43353.1.
    M17813 Genomic RNA. Translation: AAA43574.1.
    PIRiA00884. NMIV9.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M11445 Genomic RNA. Translation: AAA43353.1 .
    M17813 Genomic RNA. Translation: AAA43574.1 .
    PIRi A00884. NMIV9.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1A14 X-ray 2.50 N 83-470 [» ]
    1BJI X-ray 2.00 A 83-470 [» ]
    1F8B X-ray 1.80 A 83-470 [» ]
    1F8C X-ray 1.70 A 83-470 [» ]
    1F8D X-ray 1.40 A 83-470 [» ]
    1F8E X-ray 1.40 A 83-470 [» ]
    1INY X-ray 2.40 A 83-470 [» ]
    1L7F X-ray 1.80 A 83-470 [» ]
    1L7G X-ray 1.85 A 83-470 [» ]
    1L7H X-ray 1.85 A 83-470 [» ]
    1MWE X-ray 1.70 A 83-470 [» ]
    1NCA X-ray 2.50 N 82-470 [» ]
    1NCB X-ray 2.50 N 82-470 [» ]
    1NCC X-ray 2.50 N 82-470 [» ]
    1NMC X-ray 2.50 A/N 83-470 [» ]
    1NNA X-ray 2.50 A 84-470 [» ]
    1NNB X-ray 2.80 A 84-470 [» ]
    1NNC X-ray 1.80 A 83-470 [» ]
    1XOE X-ray 2.20 A 84-470 [» ]
    1XOG X-ray 2.80 A 84-470 [» ]
    2C4A X-ray 2.15 A 83-470 [» ]
    2C4L X-ray 2.15 A 83-470 [» ]
    2QWA X-ray 1.70 A 83-470 [» ]
    2QWB X-ray 2.00 A 83-470 [» ]
    2QWC X-ray 1.60 A 83-470 [» ]
    2QWD X-ray 2.00 A 83-470 [» ]
    2QWE X-ray 2.00 A 83-470 [» ]
    2QWF X-ray 1.90 A 83-470 [» ]
    2QWG X-ray 1.80 A 83-470 [» ]
    2QWH X-ray 1.80 A 83-470 [» ]
    2QWI X-ray 2.00 A 83-470 [» ]
    2QWJ X-ray 2.00 A 83-470 [» ]
    2QWK X-ray 1.80 A 83-470 [» ]
    3NN9 X-ray 2.30 A 83-470 [» ]
    3W09 X-ray 2.00 A 83-470 [» ]
    4DGR X-ray 1.55 A 82-470 [» ]
    4NN9 X-ray 2.30 A 83-470 [» ]
    5NN9 X-ray 2.30 A 83-470 [» ]
    6NN9 X-ray 2.30 A 83-470 [» ]
    7NN9 X-ray 2.00 A 83-470 [» ]
    ProteinModelPortali P03472.
    SMRi P03472. Positions 82-470.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P03472.

    Protein family/group databases

    CAZyi GH34. Glycoside Hydrolase Family 34.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P03472.

    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. "Gene and protein sequence of an influenza neuraminidase with hemagglutinin activity."
      Air G.M., Ritchie L.R., Laver W.G., Colman P.M.
      Virology 145:117-122(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "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].
    3. "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.
    4. "Neuraminidase inhibitors for influenza."
      Moscona A.
      N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    5. "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.
    6. "Three-dimensional structure of neuraminidase of subtype N9 from an avian influenza virus."
      Baker A.T., Varghese J.N., Laver W.G., Air G.M., Colman P.M.
      Proteins 2:111-117(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 83-470.
    7. "Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid."
      Bossart-Whitaker P., Carson M., Babu Y.S., Smith C.D., Laver W.G., Air G.M.
      J. Mol. Biol. 232:1069-1083(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 83-470 IN COMPLEX WITH CALCIUM AND SUBSTRATE ANALOG, DISULFIDE BOND, ACTIVE SITE, COFACTOR, SUBUNIT.
    8. "Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase."
      Varghese J.N., Epa V.C., Colman P.M.
      Protein Sci. 4:1081-1087(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 83-470 IN COMPLEX WITH CALCIUM AND SUBSTRATE ANALOG, COFACTOR, DISULFIDE BOND, SUBUNIT, GLYCOSYLATION AT ASN-87; ASN-147 AND ASN-202.
    9. "Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases."
      Varghese J.N., Colman P.M., van Donkelaar A., Blick T.J., Sahasrabudhe A., McKimm-Breschkin J.L.
      Proc. Natl. Acad. Sci. U.S.A. 94:11808-11812(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 83-470 IN COMPLEX WITH CALCIUM, COFACTOR, ACTIVE SITE, DISULFIDE BOND, GLYCOSYLATION AT ASN-87; ASN-147 AND ASN-202.
    10. "Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity."
      Kim J.H., Resende R., Wennekes T., Chen H.M., Bance N., Buchini S., Watts A.G., Pilling P., Streltsov V.A., Petric M., Liggins R., Barrett S., McKimm-Breschkin J.L., Niikura M., Withers S.G.
      Science 340:71-75(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 83-470 IN COMPLEX WITH CALCIUM AND SUBSTRATE ANALOG, CATALYTIC ACTIVITY, ACTIVE SITE, IDENTIFICATION BY MASS SPECTROMETRY, COFACTOR, ENZYME REGULATION, DISULFIDE BOND, GLYCOSYLATION AT ASN-87; ASN-147 AND ASN-202.

    Entry informationi

    Entry nameiNRAM_I75A5
    AccessioniPrimary (citable) accession number: P03472
    Secondary accession number(s): Q84070
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 21, 1986
    Last modified: October 1, 2014
    This is version 120 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