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P03470

- NRAM_I33A0

UniProt

P03470 - NRAM_I33A0

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Protein

Neuraminidase

Gene
NA
Organism
Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript 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.1 Publication
Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious.1 Publication

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 sitei102 – 1021Substrate By similarity
Active sitei135 – 1351Proton donor/acceptor By similarity
Binding sitei136 – 1361Substrate By similarity
Binding sitei277 – 2771Substrate By similarity
Metal bindingi278 – 2781Calcium; via carbonyl oxygen By similarity
Metal bindingi282 – 2821Calcium; via carbonyl oxygen By similarity
Metal bindingi308 – 3081Calcium By similarity
Metal bindingi328 – 3281Calcium; via carbonyl oxygen By similarity
Binding sitei352 – 3521Substrate By similarity
Active sitei386 – 3861Nucleophile 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/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Taxonomic identifieri381518 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000000834: Genome

Subcellular locationi

Virion membrane. Host apical cell membrane; Single-pass type II membrane protein
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.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66Intravirion Reviewed prediction
Transmembranei7 – 3529Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini36 – 453418Virion surface Reviewed predictionAdd
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 – 453453NeuraminidasePRO_0000078726Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi44 – 441N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi72 – 721N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi76 ↔ 401 By similarity
Disulfide bondi108 ↔ 113 By similarity
Glycosylationi130 – 1301N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi168 ↔ 215 By similarity
Disulfide bondi217 ↔ 222 By similarity
Glycosylationi219 – 2191N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi263 ↔ 276 By similarity
Disulfide bondi265 ↔ 274 By similarity
Disulfide bondi302 ↔ 319 By similarity
Disulfide bondi405 ↔ 430 By similarity

Post-translational modificationi

N-glycosylated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.

Structurei

3D structure databases

ProteinModelPortaliP03470.
SMRiP03470. Positions 67-451.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft associationAdd
BLAST
Regioni36 – 7439Hypervariable stalk regionAdd
BLAST
Regioni75 – 453379Head of neuraminidaseAdd
BLAST
Regioni261 – 2622Substrate binding By similarity

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.

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.

P03470-1 [UniParc]FASTAAdd to Basket

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MNPNQKIITI GSICMVVGII SLILQIGNII SIWISHSIQT GNQNHTGICN    50
QGIITYNVVA GQDSTSVILT GNSSLCPIRG WAIHSKDNGI RIGSKGDVFV 100
IREPFISCSH LECRTFFLTQ GALLNDKHSN GTVKDRSPYR ALMSCPVGEA 150
PSPYNSRFES VAWSASACHD GMGWLTIGIS GPDNGAVAVL KYNGIITETI 200
KSWRKKILRT QESECTCVNG SCFTIMTDGP SNGLASYKIF KIEKGKVTKS 250
IELNAPNSHY EECSCYPDTG KVMCVCRDNW HGSNRPWVSF DQNLDYQIGY 300
ICSGVFGDNP RPKDGPGSCG PVSADGANGV KGFSYRYGNG VWIGRTKSDS 350
SRHGFEMIWD PNGWTETDSR FSVRQDVVAM TDRSGYSGSF VQHPELTGLD 400
CMRPCFWVEL IRGRPEEETI WTSGSIISFC GVNSDTVDWS WPDGAELPFT 450
IDK 453
Length:453
Mass (Da):49,687
Last modified:December 20, 2005 - v2
Checksum:i76E63E3A97D1EFEC
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti53 – 531I → S in strain: A/WSN/33.
Natural varianti56 – 572YN → HK in strain: A/NWS/33.
Natural varianti57 – 571N → K in strain: A/WSN/33.
Natural varianti130 – 1301N → R in strain: A/WSN/33.
Natural varianti130 – 1301N → Y in strain: A/NWS/33.
Natural varianti133 – 1331V → F in strain: A/WSN/33.
Natural varianti133 – 1331V → S in strain: A/NWS/33.
Natural varianti184 – 1841N → D in strain: A/WSN/33.
Natural varianti206 – 2061K → N in strain: A/WSN/33.
Natural varianti232 – 2321N → D in strain: A/WSN/33 and A/NWS/33.
Natural varianti297 – 2971Q → K in strain: A/WSN/33.
Natural varianti316 – 3161P → T in strain: A/WSN/33 and A/NWS/33.
Natural varianti336 – 3361R → K in strain: A/WSN/33.
Natural varianti373 – 3731V → M in strain: A/WSN/33.
Natural varianti414 – 4141R → L in strain: A/WSN/33.
Natural varianti414 – 4141R → Q in strain: A/NWS/33.
Natural varianti418 – 4192ET → DA in strain: A/WSN/33.
Natural varianti434 – 4341S → G in strain: A/WSN/33.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti172 – 1721M → V in AAA43397. 1 Publication
Sequence conflicti380 – 3823MTD → ITN in AAA43397. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02177 Genomic RNA. Translation: AAA43397.1. Sequence problems.
L25815 mRNA. Translation: AAA91326.1.
L25816 mRNA. Translation: AAA91327.1.
L25817 mRNA. Translation: AAA91328.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02177 Genomic RNA. Translation: AAA43397.1 . Sequence problems.
L25815 mRNA. Translation: AAA91326.1 .
L25816 mRNA. Translation: AAA91327.1 .
L25817 mRNA. Translation: AAA91328.1 .

3D structure databases

ProteinModelPortali P03470.
SMRi P03470. Positions 67-451.
ModBasei Search...
MobiDBi Search...

Chemistry

ChEMBLi CHEMBL1287610.

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. "Complete nucleotide sequence of the neuraminidase gene of human influenza virus A/WSN/33."
    Hiti A.L., Nayak D.P.
    J. Virol. 41:730-734(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: A/WSN/33.
  2. "Changes in the neuraminidase of neurovirulent influenza virus strains."
    Ward A.C.
    Virus Genes 10:253-260(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: A/NWS/33, A/WS/33 and A/WSN/33.
  3. "Analysis of the transmembrane domain of influenza virus neuraminidase, a type II transmembrane glycoprotein, for apical sorting and raft association."
    Barman S., Nayak D.P.
    J. Virol. 74:6538-6545(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  4. "Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication."
    Suzuki T., Takahashi T., Guo C.T., Hidari K.I., Miyamoto D., Goto H., Kawaoka Y., Suzuki Y.
    J. Virol. 79:11705-11715(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: A/WSN/33.
  5. "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.
  6. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  7. "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_I33A0
AccessioniPrimary (citable) accession number: P03470
Secondary accession number(s): Q67215, Q67216, Q67217
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 20, 2005
Last modified: September 3, 2014
This is version 104 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

Complete proteome

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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