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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Equine/Kentucky/1/1981)
Status
Reviewed-Annotation score: 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

Ca2+By similarityNote: Binds 1 Ca2+ 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)DescriptionActionsGraphical viewLength
Binding sitei116SubstrateBy similarity1
Active sitei149Proton donor/acceptorBy similarity1
Binding sitei150SubstrateBy similarity1
Binding sitei291SubstrateBy similarity1
Metal bindingi292Calcium; via carbonyl oxygenBy similarity1
Metal bindingi296Calcium; via carbonyl oxygenBy similarity1
Metal bindingi322CalciumBy similarity1
Binding sitei368SubstrateBy similarity1
Active sitei402NucleophileBy similarity1

GO - Molecular functioni

GO - Biological processi

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/Equine/Kentucky/1/1981)
Taxonomic identifieri475467 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Equus caballus (Horse) [TaxID: 9796]

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6IntravirionSequence analysis6
Transmembranei7 – 35Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST29

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000786971 – 470NeuraminidaseAdd BLAST470

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi46N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi54N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi84N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi90 ↔ 417By similarity
Disulfide bondi122 ↔ 127By similarity
Glycosylationi144N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi182 ↔ 229By similarity
Disulfide bondi231 ↔ 236By similarity
Disulfide bondi277 ↔ 290By similarity
Disulfide bondi279 ↔ 288By similarity
Glycosylationi293N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi316 ↔ 335By similarity
Glycosylationi398N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi421 ↔ 446By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

3D structure databases

ProteinModelPortaliP08326.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationBy similarityAdd BLAST23
Regioni39 – 88Hypervariable stalk regionAdd BLAST50
Regioni89 – 470Head of neuraminidaseAdd BLAST382
Regioni275 – 276Substrate bindingBy similarity2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi439 – 442Poly-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 (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.

P08326-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKIIAI GSASLGILIL NVILHVVSII VTVLVLNNNG TGLNCNGTII
60 70 80 90 100
REYNETVRVE RITQWYNTNT IEYIERPSNE YYMNNTEPLC EAQGFAPFSK
110 120 130 140 150
DNGIRIGSRG HVFVIREPFV SCSPLECRTF FLTQGSLLND KHSNGTVKDR
160 170 180 190 200
SPYRTLMSVK VGQSPNVYQA RFESVAWSAT ACHDGKKWMT VGVTGPDNQA
210 220 230 240 250
VAVVNYGGVP VDIINSWGRD ILRTQESSCT CIKGDCYWVM TDGPANRQAK
260 270 280 290 300
YRIFKAKDGR IIGQTDISFN GGHIEECSCY PNEGKVECVC RDNWTGTNRP
310 320 330 340 350
ILVISPDLSY TVGYLCAGIP TDTPRGEDSQ FTGSCTSPLG NKGYGVKGFG
360 370 380 390 400
FRQGNDVWAG RTISRTSRSG FEIIKIRNGW TQNSKDQIRK QVIIDNLNWS
410 420 430 440 450
GYSGSFTLPV ELTKKGCLVP CFWVEMIRGK PEDTTIWTSS SSIVMCGVDH
460 470
KIASWSWHDG AILPFDIDKI
Length:470
Mass (Da):52,171
Last modified:August 1, 1988 - v1
Checksum:iE71AAB9C31538A7A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14917 Genomic RNA. Translation: AAA43245.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14917 Genomic RNA. Translation: AAA43245.1.

3D structure databases

ProteinModelPortaliP08326.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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.
ProtoNetiSearch...

Entry informationi

Entry nameiNRAM_I81A2
AccessioniPrimary (citable) accession number: P08326
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: October 5, 2016
This is version 108 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

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.