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P06820

- NRAM_I67A0

UniProt

P06820 - NRAM_I67A0

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Protein
Neuraminidase
Gene
NA
Organism
Influenza A virus (strain A/Tokyo/3/1967 H2N2)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 sitei118 – 1181Substrate
Active sitei151 – 1511Proton donor/acceptor By similarity
Binding sitei152 – 1521Substrate
Binding sitei292 – 2921Substrate
Metal bindingi293 – 2931Calcium; via carbonyl oxygen
Metal bindingi297 – 2971Calcium; via carbonyl oxygen
Metal bindingi324 – 3241Calcium
Metal bindingi345 – 3451Calcium; via carbonyl oxygen
Metal bindingi346 – 3461Calcium; via carbonyl oxygen
Metal bindingi347 – 3471Calcium; via carbonyl oxygen
Binding sitei371 – 3711Substrate
Active sitei406 – 4061Nucleophile By 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
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

SABIO-RKP06820.

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/Tokyo/3/1967 H2N2)
Taxonomic identifieri380960 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]

Subcellular locationi

Virion membrane By similarity. Host apical cell membrane; 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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66Intravirion Reviewed prediction
Transmembranei7 – 3529Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST
Topological domaini36 – 469434Virion surface Reviewed prediction
Add
BLAST

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
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 469469Neuraminidase
PRO_0000078720Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi61 – 611N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi69 – 691N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi70 – 701N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi86 – 861N-linked (GlcNAc...); by host
Disulfide bondi92 ↔ 417
Disulfide bondi124 ↔ 129
Glycosylationi146 – 1461N-linked (GlcNAc...); by host
Disulfide bondi175 ↔ 193
Disulfide bondi183 ↔ 230
Glycosylationi200 – 2001N-linked (GlcNAc...); by host
Disulfide bondi232 ↔ 237
Glycosylationi234 – 2341N-linked (GlcNAc...); by host
Disulfide bondi278 ↔ 291
Disulfide bondi280 ↔ 289
Disulfide bondi318 ↔ 337
Disulfide bondi421 ↔ 447

Post-translational modificationi

N-glycosylated.

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi96 – 1027
Helixi105 – 1084
Turni109 – 1113
Beta strandi121 – 1244
Beta strandi129 – 1324
Beta strandi137 – 1393
Turni144 – 1496
Beta strandi157 – 1626
Beta strandi172 – 1765
Beta strandi178 – 1847
Beta strandi186 – 19611
Beta strandi198 – 20710
Beta strandi210 – 2167
Beta strandi218 – 2214
Beta strandi227 – 2293
Beta strandi231 – 2333
Beta strandi236 – 2449
Beta strandi246 – 2483
Beta strandi250 – 26718
Beta strandi276 – 2816
Beta strandi284 – 2929
Beta strandi294 – 2963
Beta strandi301 – 3055
Turni307 – 3093
Beta strandi312 – 3165
Beta strandi319 – 3213
Beta strandi324 – 3263
Beta strandi330 – 3323
Beta strandi337 – 3393
Beta strandi353 – 3564
Beta strandi359 – 3668
Beta strandi368 – 3714
Beta strandi374 – 3818
Turni382 – 3843
Beta strandi385 – 3873
Beta strandi390 – 3934
Beta strandi407 – 4137
Beta strandi415 – 42915
Turni430 – 4323
Beta strandi435 – 4373
Beta strandi439 – 45113
Turni464 – 4663

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1INGX-ray2.40A/B82-469[»]
1INHX-ray2.40A/B82-469[»]
1INWX-ray2.40A82-469[»]
1INXX-ray2.40A82-469[»]
1IVCX-ray2.40A/B82-469[»]
1IVDX-ray1.90A/B82-469[»]
1IVEX-ray2.40A/B82-469[»]
1IVFX-ray2.40A/B82-469[»]
1IVGX-ray1.90A/B82-469[»]
1NN2X-ray2.20A82-469[»]
2BATX-ray2.00A82-469[»]
ProteinModelPortaliP06820.
SMRiP06820. Positions 82-469.

Miscellaneous databases

EvolutionaryTraceiP06820.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft association By similarity
Add
BLAST
Regioni36 – 9055Hypervariable stalk region
Add
BLAST
Regioni91 – 469379Head of neuraminidase
Add
BLAST
Regioni276 – 2772Substrate binding By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi179 – 1824Poly-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.

Sequence similaritiesi

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.

P06820-1 [UniParc]FASTAAdd to Basket

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MNPNQKIITI GSVSLTIATV CFLMQIAILV TTVTLHFKQH ECDSPASNQV    50
MPCEPIIIER NITEIVYLNN TTIEKEICPK VVEYRNWSKP QCQITGFAPF 100
SKDNSIRLSA GGDIWVTREP YVSCDPVKCY QFALGQGTTL DNKHSNDTVH 150
DRIPHRTLLM NELGVPFHLG TRQVCIAWSS SSCHDGKAWL HVCITGDDKN 200
ATASFIYDGR LVDSIGSWSQ NILRTQESEC VCINGTCTVV MTDGSASGRA 250
DTRILFIEEG KIVHISPLAG SAQHVEECSC YPRYPGVRCI CRDNWKGSNR 300
PVVDINMEDY SIDSSYVCSG LVGDTPRNDD RSSNSNCRNP NNERGTQGVK 350
GWAFDNGNDL WMGRTISKDL RSGYETFKVI GGWSTPNSKS QINRQVIVDS 400
DNRSGYSGIF SVEGKSCINR CFYVELIRGR KQETRVWWTS NSIVVFCGTS 450
GTYGTGSWPD GANINFMPI 469
Length:469
Mass (Da):52,131
Last modified:October 1, 1996 - v2
Checksum:iDF9F74BFFA3FEBC9
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti41 – 411E → D in AAO46245. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K01393 Genomic RNA. Translation: AAB05621.1.
AY209929 Genomic RNA. Translation: AAO46245.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K01393 Genomic RNA. Translation: AAB05621.1 .
AY209929 Genomic RNA. Translation: AAO46245.1 .

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1ING X-ray 2.40 A/B 82-469 [» ]
1INH X-ray 2.40 A/B 82-469 [» ]
1INW X-ray 2.40 A 82-469 [» ]
1INX X-ray 2.40 A 82-469 [» ]
1IVC X-ray 2.40 A/B 82-469 [» ]
1IVD X-ray 1.90 A/B 82-469 [» ]
1IVE X-ray 2.40 A/B 82-469 [» ]
1IVF X-ray 2.40 A/B 82-469 [» ]
1IVG X-ray 1.90 A/B 82-469 [» ]
1NN2 X-ray 2.20 A 82-469 [» ]
2BAT X-ray 2.00 A 82-469 [» ]
ProteinModelPortali P06820.
SMRi P06820. Positions 82-469.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P06820.

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Enzyme and pathway databases

SABIO-RK P06820.

Miscellaneous databases

EvolutionaryTracei P06820.
PROi P06820.

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. "Sequence of the neuraminidase gene of influenza virus A/Tokyo/3/67 and previously uncharacterized monoclonal variants."
    Lentz M.R., Air G.M., Laver W.G., Webster R.G.
    Virology 135:257-265(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Air G.M.
    Submitted (JUL-1996) to UniProtKB
    Cited for: SEQUENCE REVISION TO 420.
  3. "Genetic analysis of human H2N2 and early H3N2 influenza viruses, 1957-1972: evidence for genetic divergence and multiple reassortment events."
    Lindstrom S.E., Cox N.J., Klimov A.
    Virology 328:101-119(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  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.
  7. "Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2-A resolution."
    Varghese J.N., Colman P.M.
    J. Mol. Biol. 221:473-486(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 82-469 IN COMPLEX WITH CALCIUM, GLYCOSYLATION AT ASN-86; ASN-146 AND ASN-200, COFACTOR, SUBUNIT, DISULFIDE BOND.
  8. "A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies."
    White C.L., Janakiraman M.N., Laver W.G., Philippon C., Vasella A., Air G.M., Luo M.
    J. Mol. Biol. 245:623-634(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 82-469 IN COMPLEX WITH SUBSTRATE ANALOG AND CALCIUM, GLYCOSYLATION AT ASN-86; ASN-146; ASN-200 AND ASN-234, COFACTOR, SUBUNIT, DISULFIDE BOND.
  9. "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 (1.90 ANGSTROMS) OF 82-469 IN COMPLEX WITH 2-DEOXY-2,3-DEHYDRO-N-ACETYL-NEURAMINIC ACID AND CALCIUM, DISULFIDE BONDS, GLYCOSYLATION AT ASN-86; ASN-146; ASN-200 AND ASN-234, COFACTOR.

Entry informationi

Entry nameiNRAM_I67A0
AccessioniPrimary (citable) accession number: P06820
Secondary accession number(s): Q6XUB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: October 1, 1996
Last modified: September 3, 2014
This is version 112 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.

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

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