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Q9WAA1

- NRAM_I97A0

UniProt

Q9WAA1 - NRAM_I97A0

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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Chicken/Hong Kong/220/1997 H5N1 genotype Gs/Gd)
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 sitei99 – 991SubstrateBy similarity
Active sitei132 – 1321Proton donor/acceptorBy similarity
Binding sitei133 – 1331SubstrateBy similarity
Binding sitei274 – 2741SubstrateBy similarity
Metal bindingi275 – 2751Calcium; via carbonyl oxygenBy similarity
Metal bindingi279 – 2791Calcium; via carbonyl oxygenBy similarity
Metal bindingi305 – 3051CalciumBy similarity
Binding sitei349 – 3491SubstrateBy similarity
Active sitei383 – 3831NucleophileBy 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/Chicken/Hong Kong/220/1997 H5N1 genotype Gs/Gd)
Taxonomic identifieri100834 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Felis catus (Cat) (Felis silvestris catus) [TaxID: 9685]
Homo sapiens (Human) [TaxID: 9606]
Panthera pardus (Leopard) (Felis pardus) [TaxID: 9691]
Panthera tigris (Tiger) [TaxID: 9694]
Sus scrofa (Pig) [TaxID: 9823]

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-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. virion membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 450450NeuraminidasePRO_0000280123Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi50 – 501N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi69 – 691N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi73 ↔ 398By similarity
Disulfide bondi105 ↔ 110By similarity
Glycosylationi127 – 1271N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi165 ↔ 212By similarity
Disulfide bondi214 ↔ 219By similarity
Glycosylationi216 – 2161N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi260 ↔ 273By similarity
Disulfide bondi262 ↔ 271By similarity
Disulfide bondi299 ↔ 316By similarity
Disulfide bondi402 ↔ 427By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ9WAA1.
SMRiQ9WAA1. Positions 64-448.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66IntravirionSequence Analysis
Topological domaini28 – 450423Virion surfaceSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei7 – 2721Helical; 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 – 7136Hypervariable stalk regionBy similarityAdd
BLAST
Regioni72 – 450379Head of neuraminidaseBy similarityAdd
BLAST
Regioni258 – 2592Substrate bindingBy 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 (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.

Q9WAA1-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSICMVVGII SLMLQIGNII SVWVSHIIQT WHPNQPEPCN
60 70 80 90 100
QSINFYTEQA AASVTLAGNS SLCPISGWAI YSKDNSIRIG SKGDVFVIRE
110 120 130 140 150
PFISCSHLEC RTFFLTQGAL LNDKHSNGTV KDRSPYRTLM SCPVGEAPSP
160 170 180 190 200
YKSRFESVAW SASACHDGIS WLTIGISGPD NGAVAVLKYN GIITDTIKSW
210 220 230 240 250
RNNILRTQES ECACVNGSCF TVMTDGPSNE QASYKIFKIE KGRVVKSVEL
260 270 280 290 300
NAPNYHYEEC SCYPDAGEIT CVCRDNWHGS NRPWVSFNQN LEYQIGYICS
310 320 330 340 350
GVFGDSPRPN DGTGSCGPVS LNGAYGVKGF SFKYGNGVWI GRTKSTSSRS
360 370 380 390 400
GFEMIWDPNG WTETDSSFSL KQDIIAITDW SGYSGSFIQH PELTGLNCMR
410 420 430 440 450
PCFWVELIRG RPKEKTIWTS GSSISFCGVN SDTVGWSWPD GAELPFTIDK
Length:450
Mass (Da):49,531
Last modified:November 1, 1999 - v1
Checksum:i7E13E0EDE7A3CF3A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti152 – 1521K → N.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF046081 Genomic RNA. Translation: AAC32079.1.
AF098547 Genomic RNA. Translation: AAF02310.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF046081 Genomic RNA. Translation: AAC32079.1 .
AF098547 Genomic RNA. Translation: AAF02310.1 .

3D structure databases

ProteinModelPortali Q9WAA1.
SMRi Q9WAA1. Positions 64-448.
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. "Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong."
    Suarez D.L., Perdue M.L., Cox N., Rowe T., Bender C., Huang J., Swayne D.E.
    J. Virol. 72:6678-6688(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Rapid evolution of H5N1 influenza viruses in chickens in Hong Kong."
    Zhou N.N., Shortridge K.F., Claas E.C.J., Krauss S.L., Webster R.G.
    J. Virol. 73:3366-3374(1999) [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.

Entry informationi

Entry nameiNRAM_I97A0
AccessioniPrimary (citable) accession number: Q9WAA1
Secondary accession number(s): Q9PZN0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: November 1, 1999
Last modified: October 29, 2014
This is version 78 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

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