Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Gull/Maryland/704/1977 H13N6)
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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei119 – 1191SubstrateBy similarity
Active sitei152 – 1521Proton donor/acceptorBy similarity
Binding sitei153 – 1531SubstrateBy similarity
Binding sitei294 – 2941SubstrateBy similarity
Metal bindingi295 – 2951Calcium; via carbonyl oxygenBy similarity
Metal bindingi299 – 2991Calcium; via carbonyl oxygenBy similarity
Metal bindingi326 – 3261CalciumBy similarity
Binding sitei373 – 3731SubstrateBy similarity
Active sitei407 – 4071NucleophileBy similarity

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/Gull/Maryland/704/1977 H13N6)
Taxonomic identifieri384499 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
ProteomesiUP000000828 Componenti: Genome

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66IntravirionSequence Analysis
Transmembranei7 – 2721Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini28 – 471444Virion surfaceSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 471471NeuraminidasePRO_0000280133Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi51 – 511N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi54 – 541N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi63 – 631N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi68 – 681N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi71 – 711N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi87 – 871N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi93 ↔ 420By similarity
Disulfide bondi125 ↔ 130By similarity
Glycosylationi147 – 1471N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi177 ↔ 195By similarity
Disulfide bondi185 ↔ 232By similarity
Glycosylationi202 – 2021N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi234 ↔ 239By similarity
Disulfide bondi280 ↔ 293By similarity
Disulfide bondi282 ↔ 291By similarity
Disulfide bondi320 ↔ 338By similarity
Glycosylationi403 – 4031N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi424 ↔ 450By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ6XV23.
SMRiQ6XV23. Positions 83-471.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft associationBy similarityAdd
BLAST
Regioni36 – 9156Hypervariable stalk regionBy similarityAdd
BLAST
Regioni92 – 471380Head of neuraminidaseBy similarityAdd
BLAST
Regioni278 – 2792Substrate bindingBy similarity

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.

Q6XV23-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKIICI SATGMTLSVV SLLIGIANLG LNIGLHYKVG DTPDVNTPNV
60 70 80 90 100
NGTNSTTTTI INNNTQNNFT NITNIIHNKN EERTFLNLTK PLCEVNSWHI
110 120 130 140 150
LSKDNAIRIG EEAHILVTRE PYLSCDPQGC RMFALSQGTT LRGRHANGTI
160 170 180 190 200
HDRSPFRALV SWEMGQAPSP YNAKIECIGW SSTSCHDGIS RMSICMSGPN
210 220 230 240 250
NNASAVVWYG GRPVTEIPSW AGNILRTQES ECVCHKGICP VVMTDGPANN
260 270 280 290 300
KAATKIIYFK EGKIQKIEEL TGNAQHIEEC SCYGAKEVIK CICRDNWKGA
310 320 330 340 350
NRPVITIDPE MMTHTSKYLC SKILTDTSRP NDPTNGNCDA PITGGNPDPG
360 370 380 390 400
VKGFAFLDGE NSWLGRTISK DSRSGYEMLK VPNAETNTQS GPITHQVIVN
410 420 430 440 450
NQNWSGYSGA FIDYWANKEC FNPCFYVELI RGRPKESSVL WTSNSIVALC
460 470
GSKERLGSWS WHDGAEIIYF K
Length:471
Mass (Da):51,888
Last modified:July 5, 2004 - v1
Checksum:i806ED70D97E7AA78
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY207553 Genomic DNA. Translation: AAO62067.1.
CY014696 Genomic RNA. Translation: ABI84569.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY207553 Genomic DNA. Translation: AAO62067.1.
CY014696 Genomic RNA. Translation: ABI84569.1.

3D structure databases

ProteinModelPortaliQ6XV23.
SMRiQ6XV23. Positions 83-471.
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...

Publicationsi

  1. "Genetic analysis of multiple N3, N4, and N6 influenza A virus neuraminidase genes."
    Webby R.J., Humberd J.L., Krauss S.L.
    Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Assembly and budding of influenza virus."
    Nayak D.P., Hui E.K., Barman S.
    Virus Res. 106:147-165(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  4. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  5. "Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses."
    Suzuki Y.
    Biol. Pharm. Bull. 28:399-408(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiNRAM_I77AF
AccessioniPrimary (citable) accession number: Q6XV23
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: July 5, 2004
Last modified: June 24, 2015
This is version 66 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.

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

External Data

Dasty 3

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 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.