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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Herring gull/DE/677/1988 H2N8)
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 sitei116 – 1161SubstrateBy similarity
Active sitei149 – 1491Proton donor/acceptorBy similarity
Binding sitei150 – 1501SubstrateBy similarity
Binding sitei291 – 2911SubstrateBy similarity
Metal bindingi292 – 2921Calcium; via carbonyl oxygenBy similarity
Metal bindingi296 – 2961Calcium; via carbonyl oxygenBy similarity
Metal bindingi322 – 3221CalciumBy similarity
Binding sitei368 – 3681SubstrateBy similarity
Active sitei402 – 4021NucleophileBy 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/Herring gull/DE/677/1988 H2N8)
Taxonomic identifieri387243 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]

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 – 3529Helical; Signal-anchor for type II membrane proteinSequence 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 – 470470NeuraminidasePRO_0000078695Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi46 – 461N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi54 – 541N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi84 – 841N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi90 ↔ 417By similarity
Disulfide bondi122 ↔ 127By similarity
Glycosylationi144 – 1441N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi182 ↔ 229By similarity
Disulfide bondi231 ↔ 236By similarity
Disulfide bondi277 ↔ 290By similarity
Disulfide bondi279 ↔ 288By similarity
Glycosylationi293 – 2931N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi316 ↔ 335By similarity
Glycosylationi398 – 3981N-linked (GlcNAc...); by hostSequence Analysis
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

ProteinModelPortaliQ07577.
SMRiQ07577. Positions 82-467.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft associationBy similarityAdd
BLAST
Regioni39 – 8850Hypervariable stalk regionAdd
BLAST
Regioni89 – 470382Head of neuraminidaseAdd
BLAST
Regioni275 – 2762Substrate bindingBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi439 – 4424Poly-Ser

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.

Q07577-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSVSLGLVVL NILLHIVSIT ITVLVLPGNG NNPSCNETVI
60 70 80 90 100
REYNETVRIE RVTQWHNTNV IEYLERPESD HFMNNTESLC DAKGFAPFSK
110 120 130 140 150
DNGIRIGSRG HVFVIREPFV SCSPTECRTF FLTQGSLLND KHSNGTVKDR
160 170 180 190 200
SPYRTLMSVQ IGQSPNVYQA RFEAVAWSAT ACHDGKKWMT IGVTGPDAKA
210 220 230 240 250
VAVVHYGGIP TDVINSWAGD ILRTQESSCT CIQGECYWVM TDGPANRQAQ
260 270 280 290 300
YRAFKAKQGK IIGQTEISFN GGHIEECSCY PNEGKVECVC RDNWTGTNRP
310 320 330 340 350
VLVISPDLSY RVGYLCAGLP SDTPRGEDSQ FTGSCTSPMG NQGYGVKGFG
360 370 380 390 400
FRQGNDVWMG RTISRTSRSG FEILKVRNGW VQNSKEQIKR QVVVDNLNWS
410 420 430 440 450
GYSGSFTLPV ELTKRNCLVP CFWVEMIRGK PEEKTIWTSS SSIVMCGVDH
460 470
EIADWSWHDG AILPFDIDKM
Length:470
Mass (Da):52,265
Last modified:February 1, 1995 - v1
Checksum:i28AF0B75E80539B7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06585 Genomic RNA. Translation: AAA43368.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06585 Genomic RNA. Translation: AAA43368.1.

3D structure databases

ProteinModelPortaliQ07577.
SMRiQ07577. Positions 82-467.
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. "Phylogenetic analysis of the N8 neuraminidase gene of influenza A viruses."
    Saito T., Kawaoka Y., Webster R.G.
    Virology 193:868-876(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "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.
  3. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  4. "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_I88A4
AccessioniPrimary (citable) accession number: Q07577
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: June 24, 2015
This is version 93 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

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.