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P03473

- NRAM_I68A6

UniProt

P03473 - NRAM_I68A6

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Protein
Neuraminidase
Gene
NA
Organism
Influenza A virus (strain A/Northern Territory/60/1968 H3N2) (Influenza A virus (strain NT60)) (Influenza A virus (strain A/NT/60/1968 H3N2))
Status
Reviewed - Annotation score: 5 out of 5 - Protein inferred from homologyi

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 sitei118 – 1181Substrate By similarity
Active sitei151 – 1511Proton donor/acceptor By similarity
Binding sitei152 – 1521Substrate By similarity
Binding sitei292 – 2921Substrate By similarity
Metal bindingi293 – 2931Calcium; via carbonyl oxygen By similarity
Metal bindingi297 – 2971Calcium; via carbonyl oxygen By similarity
Metal bindingi324 – 3241Calcium By similarity
Binding sitei371 – 3711Substrate By similarity
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

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/Northern Territory/60/1968 H3N2) (Influenza A virus (strain NT60)) (Influenza A virus (strain A/NT/60/1968 H3N2))
Taxonomic identifieri384505 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]

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_0000078710Add
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 Reviewed prediction
Disulfide bondi92 ↔ 417 By similarity
Disulfide bondi124 ↔ 129 By similarity
Glycosylationi146 – 1461N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi175 ↔ 193 By similarity
Disulfide bondi183 ↔ 230 By similarity
Glycosylationi200 – 2001N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi232 ↔ 237 By similarity
Glycosylationi234 – 2341N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi278 ↔ 291 By similarity
Disulfide bondi280 ↔ 289 By similarity
Disulfide bondi318 ↔ 337 By similarity
Glycosylationi402 – 4021N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi421 ↔ 447 By similarity

Post-translational modificationi

N-glycosylated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer By similarity.

Structurei

3D structure databases

ProteinModelPortaliP03473.
SMRiP03473. Positions 82-469.

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.

P03473-1 [UniParc]FASTAAdd to Basket

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MNPNQKIITI GSVSLTIATV CFLMQTAILV TTVTLHFKQY ECDSPASNQV    50
MPCEPIIIER NITEIVYLNN TTIEKEICPK VVEYRNWSKP QCQITGFAPF 100
SKDNSIRLSA GGDIWVTREP YVSCDHGKCY QFALGQGTTL DNKHSNDTIH 150
DRIPHRTLLM NELGVPFHLG TRQVCIAWSS SSCHDGKAWL HVCITGDDKN 200
ATASFIYDGR LVDSIGSWSQ NILRTQESEC VCINGTCTVV MTDGSASGRA 250
DTRILFIEEG KIVHISPLSG SAQHVEECSC YPRYPGVRCI CRDNWKGSNR 300
PVVDINMEDY SIDSSYVCSG LVGDTPRNDD RSSNSNCRNP NNERGNQGVK 350
GWAFDNGDDV WMGRTISKDL RSGYETFKVI GGWSTPNSKS QINRQVIVDS 400
DNRSGYSGIF SVEGKSCINR CFYVELIRGR KQEARVWWTS NSIVVFCGTS 450
GTYGTGSWPD GANINFMPI 469
Length:469
Mass (Da):52,143
Last modified:July 21, 1986 - v1
Checksum:i5BF69A81412F7DE6
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02136 Genomic RNA. Translation: AAA43399.1.
PIRiA00885. NMIV2.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02136 Genomic RNA. Translation: AAA43399.1 .
PIRi A00885. NMIV2.

3D structure databases

ProteinModelPortali P03473.
SMRi P03473. Positions 82-469.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

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 N2 neuraminidase from influenza virus A/NT/60/68."
    Bentley D.R., Brownlee G.G.
    Nucleic Acids Res. 10:5033-5042(1982) [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.

Entry informationi

Entry nameiNRAM_I68A6
AccessioniPrimary (citable) accession number: P03473
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: September 3, 2014
This is version 99 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.

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

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