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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Swine/Hong Kong/4/1976 H3N2)
Status
Reviewed-Annotation score: Annotation score: 4 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.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 sitei118SubstrateUniRule annotation1
Active sitei151Proton donor/acceptorUniRule annotation1
Binding sitei152SubstrateUniRule annotation1
Binding sitei292SubstrateUniRule annotation1
Metal bindingi293Calcium; via carbonyl oxygenUniRule annotation1
Metal bindingi297Calcium; via carbonyl oxygenUniRule annotation1
Metal bindingi324CalciumUniRule annotation1
Binding sitei371SubstrateUniRule annotation1
Active sitei406NucleophileUniRule 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/Swine/Hong Kong/4/1976 H3N2)
Taxonomic identifieri380217 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA 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 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 – 9IntravirionUniRule annotation9
Transmembranei10 – 30HelicalUniRule annotationAdd BLAST21
Topological domaini31 – 469Virion surfaceUniRule annotationAdd BLAST439

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000787281 – 469NeuraminidaseAdd BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi61N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi70N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi86N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi92 ↔ 417UniRule annotation
Disulfide bondi124 ↔ 129UniRule annotation
Glycosylationi146N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi183 ↔ 230UniRule annotation
Glycosylationi200N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi232 ↔ 237UniRule annotation
Glycosylationi234N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi278 ↔ 291UniRule annotation
Disulfide bondi280 ↔ 289UniRule annotation
Disulfide bondi318 ↔ 337UniRule annotation
Disulfide bondi421 ↔ 447UniRule annotation

Post-translational modificationi

N-glycosylated.UniRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.UniRule annotation

Structurei

3D structure databases

ProteinModelPortaliQ09105.
SMRiQ09105.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationUniRule annotationAdd BLAST23
Regioni36 – 88Hypervariable stalk regionUniRule annotationAdd BLAST53
Regioni91 – 469Head of neuraminidaseUniRule annotationAdd BLAST379
Regioni276 – 277Substrate bindingUniRule annotation2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi179 – 182Poly-Ser4
Compositional biasi332 – 335Poly-Ser4

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

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.

Q09105-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSVSLTIATI CFLMQIAILV TTVTLHFKQY ECDSPANNQV
60 70 80 90 100
MPCEPIIIER NITEIVYLTN TTIEKEICPK LVEYRNWSKP QCKITGFAPF
110 120 130 140 150
SKDNSIRLSA GGDIWVTREP YVSCDPGKCY QFALGQGTTL DNKHSNDTIH
160 170 180 190 200
DRTPHRTLLM NELGVPFHLG TRQVCIAWSS SSCHDGKAWL HVCVTGYDKN
210 220 230 240 250
ATASFIYDGR LVDSIGSWSQ NILRTQESEC VCINGTCTVV MTDGSASGRA
260 270 280 290 300
DTKILFIEEG KIVHTSPLSG SAQHVEECSC YPRYPGVRCI CRDNWKGSNR
310 320 330 340 350
PVVDINVKDY SIDSSYVCSG LVGDTPRKND RSSSSYCRNP NNEKGTHGVK
360 370 380 390 400
GWAFDDGNDV WMGRTISEDS RSGYETFKVI GGWSTPNSKL QINRQVIVDS
410 420 430 440 450
NDRSGYSGIF SVEGKSCINR CFYVELIRGR EQETRVWWTS NSIVVFCGTS
460
GTYGTGSWPD GADINLMPI
Length:469
Mass (Da):52,108
Last modified:February 1, 1995 - v1
Checksum:i58A3E9C71A3D3D9E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00716 Genomic RNA. Translation: BAA00621.1.
D21189 Genomic RNA. Translation: BAA04725.1.

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_I76AB
AccessioniPrimary (citable) accession number: Q09105
Secondary accession number(s): Q67338
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: June 7, 2017
This is version 101 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families