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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Status
Reviewed-Annotation score: Annotation score: 5 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.1 Publication
Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious.1 Publication

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 sitei102SubstrateBy similarity1
Active sitei135Proton donor/acceptorBy similarity1
Binding sitei136SubstrateBy similarity1
Binding sitei277SubstrateBy similarity1
Metal bindingi278Calcium; via carbonyl oxygenBy similarity1
Metal bindingi282Calcium; via carbonyl oxygenBy similarity1
Metal bindingi308CalciumBy similarity1
Metal bindingi328Calcium; via carbonyl oxygenBy similarity1
Binding sitei352SubstrateBy similarity1
Active sitei386NucleophileBy 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/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Taxonomic identifieri381518 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000000834 Componenti: Genome

Subcellular locationi

  • Virion membrane 1 Publication
  • Host apical cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication

  • 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.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6IntravirionSequence analysis6
Transmembranei7 – 35Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST29
Topological domaini36 – 453Virion surfaceSequence analysisAdd BLAST418

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1287610.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000787261 – 453NeuraminidaseAdd BLAST453

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi44N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi72N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi76 ↔ 401By similarity
Disulfide bondi108 ↔ 113By similarity
Glycosylationi130N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi168 ↔ 215By similarity
Disulfide bondi217 ↔ 222By similarity
Glycosylationi219N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi263 ↔ 276By similarity
Disulfide bondi265 ↔ 274By similarity
Disulfide bondi302 ↔ 319By similarity
Disulfide bondi405 ↔ 430By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.

Chemistry databases

BindingDBiP03470.

Structurei

3D structure databases

ProteinModelPortaliP03470.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationAdd BLAST23
Regioni36 – 74Hypervariable stalk regionAdd BLAST39
Regioni75 – 453Head of neuraminidaseAdd BLAST379
Regioni261 – 262Substrate bindingBy similarity2

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.

Sequence similaritiesi

Belongs to the glycosyl hydrolase 34 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

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: Complete.

P03470-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSICMVVGII SLILQIGNII SIWISHSIQT GNQNHTGICN
60 70 80 90 100
QGIITYNVVA GQDSTSVILT GNSSLCPIRG WAIHSKDNGI RIGSKGDVFV
110 120 130 140 150
IREPFISCSH LECRTFFLTQ GALLNDKHSN GTVKDRSPYR ALMSCPVGEA
160 170 180 190 200
PSPYNSRFES VAWSASACHD GMGWLTIGIS GPDNGAVAVL KYNGIITETI
210 220 230 240 250
KSWRKKILRT QESECTCVNG SCFTIMTDGP SNGLASYKIF KIEKGKVTKS
260 270 280 290 300
IELNAPNSHY EECSCYPDTG KVMCVCRDNW HGSNRPWVSF DQNLDYQIGY
310 320 330 340 350
ICSGVFGDNP RPKDGPGSCG PVSADGANGV KGFSYRYGNG VWIGRTKSDS
360 370 380 390 400
SRHGFEMIWD PNGWTETDSR FSVRQDVVAM TDRSGYSGSF VQHPELTGLD
410 420 430 440 450
CMRPCFWVEL IRGRPEEETI WTSGSIISFC GVNSDTVDWS WPDGAELPFT

IDK
Length:453
Mass (Da):49,687
Last modified:December 20, 2005 - v2
Checksum:i76E63E3A97D1EFEC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti172M → V in AAA43397 (PubMed:7077751).Curated1
Sequence conflicti380 – 382MTD → ITN in AAA43397 (PubMed:7077751).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti53I → S in strain: A/WSN/33. 1
Natural varianti56 – 57YN → HK in strain: A/NWS/33. 2
Natural varianti57N → K in strain: A/WSN/33. 1
Natural varianti130N → R in strain: A/WSN/33. 1
Natural varianti130N → Y in strain: A/NWS/33. 1
Natural varianti133V → F in strain: A/WSN/33. 1
Natural varianti133V → S in strain: A/NWS/33. 1
Natural varianti184N → D in strain: A/WSN/33. 1
Natural varianti206K → N in strain: A/WSN/33. 1
Natural varianti232N → D in strain: A/WSN/33 and A/NWS/33. 1
Natural varianti297Q → K in strain: A/WSN/33. 1
Natural varianti316P → T in strain: A/WSN/33 and A/NWS/33. 1
Natural varianti336R → K in strain: A/WSN/33. 1
Natural varianti373V → M in strain: A/WSN/33. 1
Natural varianti414R → L in strain: A/WSN/33. 1
Natural varianti414R → Q in strain: A/NWS/33. 1
Natural varianti418 – 419ET → DA in strain: A/WSN/33. 2
Natural varianti434S → G in strain: A/WSN/33. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02177 Genomic RNA. Translation: AAA43397.1. Sequence problems.
L25815 mRNA. Translation: AAA91326.1.
L25816 mRNA. Translation: AAA91327.1.
L25817 mRNA. Translation: AAA91328.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02177 Genomic RNA. Translation: AAA43397.1. Sequence problems.
L25815 mRNA. Translation: AAA91326.1.
L25816 mRNA. Translation: AAA91327.1.
L25817 mRNA. Translation: AAA91328.1.

3D structure databases

ProteinModelPortaliP03470.
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

BindingDBiP03470.
ChEMBLiCHEMBL1287610.

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_I33A0
AccessioniPrimary (citable) accession number: P03470
Secondary accession number(s): Q67215, Q67216, Q67217
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: December 20, 2005
Last modified: October 5, 2016
This is version 113 of the entry and version 2 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.

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

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.