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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Swine/Hong Kong/127/1982 H3N2)
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 sitei95SubstrateBy similarity1
Active sitei128Proton donor/acceptorBy similarity1
Binding sitei129SubstrateBy similarity1
Binding sitei269SubstrateBy similarity1
Metal bindingi270Calcium; via carbonyl oxygenBy similarity1
Metal bindingi274Calcium; via carbonyl oxygenBy similarity1
Metal bindingi301CalciumBy similarity1
Binding sitei348SubstrateBy similarity1
Active sitei383NucleophileBy 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/Swine/Hong Kong/127/1982 H3N2)
Taxonomic identifieri384483 [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 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

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002801581 – 446NeuraminidaseAdd BLAST446

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi38N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi47N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi63N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi69 ↔ 394By similarity
Disulfide bondi101 ↔ 106By similarity
Glycosylationi123N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi152 ↔ 170By similarity
Disulfide bondi160 ↔ 207By similarity
Glycosylationi177N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi209 ↔ 214By similarity
Glycosylationi211N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi255 ↔ 268By similarity
Disulfide bondi257 ↔ 266By similarity
Disulfide bondi295 ↔ 314By similarity
Glycosylationi379N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi398 ↔ 424By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ67344.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni13 – 67Hypervariable stalk regionBy similarityAdd BLAST55
Regioni68 – 446Head of neuraminidaseBy similarityAdd BLAST379
Regioni253 – 254Substrate bindingBy similarity2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi308 – 312Poly-Ser5

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

Family and domain databases

CDDicd15483. Influenza_NA. 1 hit.
Gene3Di2.120.10.10. 1 hit.
InterProiIPR001860. Glyco_hydro_34.
IPR033654. Sialidase_Influenza_A/B.
IPR011040. Sialidases.
[Graphical view]
PfamiPF00064. Neur. 1 hit.
[Graphical view]
SUPFAMiSSF50939. SSF50939. 1 hit.

Sequencei

Sequence statusi: Fragment.

Q67344-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQIAILVTTV TLHFNQYECD SLADNQVMPC EPIIIERNIT EIIYLTNTTI
60 70 80 90 100
EKEICPKLME YRNWSRPQCK ITGFAPFSKD NSIRLSAGGD IWVTREPYVS
110 120 130 140 150
CDPGKCYQFA LGQGTTLDNK HSNDTIHDRI PHRTLLMNEL GVPFHLGTRQ
160 170 180 190 200
VCIAWSSSSC HDGKAWLHVC VTGDDKNATA SFIYDGRLVD SMGSWSQNIL
210 220 230 240 250
RTQESECVCI NGTCTVVMTD GSASGRADTR ILFIEEGKIV HISPLSGSAQ
260 270 280 290 300
HVEECSCYPR YPSVRCICRD NWKGSNRPIV DINIKDYSID SRYVCSGLVG
310 320 330 340 350
DTPRNNDRSS SSDCKNPNND KGNHGVKGWA FDDGNDVWMG RTISKDSRSG
360 370 380 390 400
YETFKVIDGW STPNSKSQIN RQVIVDRDNR SGYSGIFSVE SKGCINRCFY
410 420 430 440
VELIRGRKQE TRVWWTSSSI VVFCGTSGTY GKGSWPDGAN INFMPI
Length:446
Mass (Da):49,915
Last modified:November 1, 1996 - v1
Checksum:iB3E31B09E6728A9D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21194 Genomic RNA. Translation: BAA04730.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21194 Genomic RNA. Translation: BAA04730.1.

3D structure databases

ProteinModelPortaliQ67344.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

CDDicd15483. Influenza_NA. 1 hit.
Gene3Di2.120.10.10. 1 hit.
InterProiIPR001860. Glyco_hydro_34.
IPR033654. Sialidase_Influenza_A/B.
IPR011040. Sialidases.
[Graphical view]
PfamiPF00064. Neur. 1 hit.
[Graphical view]
SUPFAMiSSF50939. SSF50939. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNRAM_I82A7
AccessioniPrimary (citable) accession number: Q67344
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: November 1, 1996
Last modified: October 5, 2016
This is version 86 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.