Skip Header

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

P03476

- NRAM_I71A2

UniProt

P03476 - NRAM_I71A2

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Turkey/Oregon/1971 H7N3)
Status
Reviewed - 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 Ca(2+) 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 sitei118 – 1181SubstrateBy similarity
Active sitei151 – 1511Proton donor/acceptorBy similarity
Binding sitei152 – 1521SubstrateBy similarity
Binding sitei293 – 2931SubstrateBy similarity
Metal bindingi294 – 2941Calcium; via carbonyl oxygenBy similarity
Metal bindingi298 – 2981Calcium; via carbonyl oxygenBy similarity
Metal bindingi324 – 3241CalciumBy similarity
Binding sitei370 – 3701SubstrateBy similarity
Active sitei405 – 4051NucleophileBy similarity

GO - Molecular functioni

  1. exo-alpha-(2->3)-sialidase activity Source: UniProtKB-EC
  2. exo-alpha-(2->6)-sialidase activity Source: UniProtKB-EC
  3. exo-alpha-(2->8)-sialidase activity Source: UniProtKB-EC
  4. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. carbohydrate metabolic process Source: InterPro
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/Turkey/Oregon/1971 H7N3)
Taxonomic identifieri385636 [NCBI]
Taxonomic lineageiVirusesssRNA 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 – 2923Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini30 – 469440Virion surfaceSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. virion membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 469469NeuraminidasePRO_0000078719Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi57 – 571N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi66 – 661N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi72 – 721N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi92 ↔ 416By similarity
Disulfide bondi124 ↔ 129By similarity
Glycosylationi146 – 1461N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi176 ↔ 194By similarity
Disulfide bondi184 ↔ 231By similarity
Disulfide bondi233 ↔ 238By similarity
Disulfide bondi280 ↔ 292By similarity
Disulfide bondi282 ↔ 290By similarity
Glycosylationi308 – 3081N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi318 ↔ 336By similarity
Disulfide bondi420 ↔ 447By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

3D structure databases

ProteinModelPortaliP03476.
SMRiP03476. Positions 88-469.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft associationBy similarityAdd
BLAST
Regioni39 – 9052Hypervariable stalk regionBy similarityAdd
BLAST
Regioni91 – 469379Head 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.

P03476-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNPNQKIITI GVVNTTLSTI ALLIGVGNLV FNTVIHEKIG NHQTVIHPTI
60 70 80 90 100
TTPAVPNCSD TIITYNNTVI NNITTTIITE AERLFKPPLP LCPFRGFFPF
110 120 130 140 150
HKDNAIRLGE NKDVIVTREP YVSCDNDNCW SFALAQGALL GTKHSNGTIK
160 170 180 190 200
DRTPYRSLIR FPIGTAPVLG NYKEICIAWS SSSCFDGKEW MHVCMTGNDN
210 220 230 240 250
DASAQIIYAG RMTDSIKSWR KDILRTQESE CQCIGGTCVV AVTDGPAANS
260 270 280 290 300
ADHRVYWIRE GRIVKYENVP KTKIQHLEEC SCYVDIDVYC ICRDNWKGSN
310 320 330 340 350
RPWMRINNET ILETGYVCSK FHSDTPRPAD PSTVSCDSPS NINGGPGVKG
360 370 380 390 400
FGFKAGNDVW LGRTVSTSGR SGFEIIKVTD GWINSPNHAK SVTQTLVSNN
410 420 430 440 450
DWSGYSGSFI VKTKGCFQPC FYVELIRGRP NKNDDVSWTS NSIVTFCGLD
460
NEPGSGNWPD GSNIGFMPK
Length:469
Mass (Da):51,790
Last modified:March 20, 2007 - v2
Checksum:i1758078B2ABE0F65
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti94 – 941F → S in CAA24276. (PubMed:6896994)Curated
Sequence conflicti94 – 941F → S in AAA43361. (PubMed:6927853)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB276110 Genomic RNA. Translation: BAF34372.1.
V01092 Genomic RNA. Translation: CAA24276.1.
K01011 Genomic RNA. Translation: AAA43361.1.
DQ870890 Genomic RNA. Translation: ABH04381.1.
DQ870896 Genomic RNA. Translation: ABH04387.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB276110 Genomic RNA. Translation: BAF34372.1 .
V01092 Genomic RNA. Translation: CAA24276.1 .
K01011 Genomic RNA. Translation: AAA43361.1 .
DQ870890 Genomic RNA. Translation: ABH04381.1 .
DQ870896 Genomic RNA. Translation: ABH04387.1 .

3D structure databases

ProteinModelPortali P03476.
SMRi P03476. Positions 88-469.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

Gene3Di 2.120.10.10. 1 hit.
InterProi IPR001860. Glyco_hydro_34.
IPR011040. Sialidases.
[Graphical view ]
Pfami PF00064. Neur. 1 hit.
[Graphical view ]
SUPFAMi SSF50939. SSF50939. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "Establishment of gene library of all haemagglutinin (HA) and neuraminidase (NA) subtypes for the control of influenza A virus infection."
    Kida H., Sakoda Y.
    Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Variation in the membrane-insertion and 'stalk' sequences in eight subtypes of influenza type A virus neuraminidase."
    Blok J., Air G.M.
    Biochemistry 21:4001-4007(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-94.
  3. "Sequence variation at the 3' end of the neuraminidase gene from 39 influenza type A viruses."
    Blok J., Air G.M.
    Virology 121:211-229(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-94.
  4. "Amelioration of influenza virus pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene."
    Cauthen A.N., Swayne D.E., Sekellick M.J., Marcus P.I., Suarez D.L.
    J. Virol. 81:1838-1847(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  5. "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.
  6. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  7. "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_I71A2
AccessioniPrimary (citable) accession number: P03476
Secondary accession number(s): Q05JI0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 20, 2007
Last modified: November 26, 2014
This is version 92 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.

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