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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
Status
Reviewed-Annotation score: Annotation score: 4 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.UniRule annotation

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.

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.UniRule annotation

Cofactori

Ca2+UniRule annotation

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.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei99SubstrateUniRule annotation1
Active sitei132Proton donor/acceptorUniRule annotation1
Binding sitei133SubstrateUniRule annotation1
Binding sitei274SubstrateUniRule annotation1
Metal bindingi275Calcium; via carbonyl oxygenUniRule annotation1
Metal bindingi279Calcium; via carbonyl oxygenUniRule annotation1
Metal bindingi305CalciumUniRule annotation1
Binding sitei349SubstrateUniRule annotation1
Active sitei383NucleophileUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGlycosidase, Hydrolase
LigandCalcium, Metal-binding

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Names & Taxonomyi

Protein namesi
Recommended name:
NeuraminidaseUniRule annotation (EC:3.2.1.18UniRule annotation)
Gene namesi
Name:NAUniRule annotation
OrganismiInfluenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
Taxonomic identifieri130763 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA 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]
Proteomesi
  • UP000008587 Componenti: Genome

Subcellular locationi

  • Virion membrane UniRule annotation
  • Host apical cell membrane UniRule annotation; Single-pass type II membrane protein UniRule annotation

  • 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.UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6IntravirionUniRule annotation6
Transmembranei7 – 27HelicalUniRule annotationAdd BLAST21
Topological domaini28 – 450Virion surfaceUniRule annotationAdd BLAST423

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000787001 – 450NeuraminidaseAdd BLAST450

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi50N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi69N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi73 ↔ 398UniRule annotation
Disulfide bondi105 ↔ 110UniRule annotation
Glycosylationi127N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi165 ↔ 212UniRule annotation
Disulfide bondi214 ↔ 219UniRule annotation
Glycosylationi216N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi260 ↔ 273UniRule annotation
Disulfide bondi262 ↔ 271UniRule annotation
Disulfide bondi299 ↔ 316UniRule annotation
Disulfide bondi402 ↔ 427UniRule annotation

Post-translational modificationi

N-glycosylated.UniRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.UniRule annotation

Structurei

3D structure databases

ProteinModelPortaliQ9W7Y7.
SMRiQ9W7Y7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationUniRule annotationAdd BLAST23
Regioni36 – 71Hypervariable stalk regionUniRule annotationAdd BLAST36
Regioni72 – 450Head of neuraminidaseUniRule annotationAdd BLAST379
Regioni258 – 259Substrate bindingUniRule annotation2

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.UniRule annotation

Sequence similaritiesi

Belongs to the glycosyl hydrolase 34 family.UniRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG0900006X.

Family and domain databases

CDDicd15483. Influenza_NA. 1 hit.
HAMAPiMF_04071. INFV_NRAM. 1 hit.
InterProiView protein in InterPro
IPR001860. Glyco_hydro_34.
IPR033654. Sialidase_Influenza_A/B.
IPR011040. Sialidases.
PfamiView protein in Pfam
PF00064. Neur. 1 hit.
SUPFAMiSSF50939. SSF50939. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9W7Y7-1 [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
YNSRFESVAW 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 GADLPFTIDK
Length:450
Mass (Da):49,503
Last modified:December 6, 2005 - v2
Checksum:i0DCB54FCB6E7C8F2
GO

Sequence cautioni

The sequence AAC34264 differs from that shown. Reason: Erroneous initiation.

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti441 – 443GAD → DAE in AAC34264 (PubMed:9430591).3
Sequence conflicti443D → E in AAC32089 (PubMed:9658115).1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF028708 mRNA. Translation: AAC40507.1.
AF036357 Genomic RNA. Translation: AAC34264.1. Different initiation.
AF046089 Genomic RNA. Translation: AAC32089.1.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiNRAM_I97A1
AccessioniPrimary (citable) accession number: Q9W7Y7
Secondary accession number(s): O89527, Q9WA99
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: June 7, 2017
This is version 96 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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