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P03468

- NRAM_I34A1

UniProt

P03468 - NRAM_I34A1

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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
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

Binds 1 calcium 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 sitei103 – 1031SubstrateBy similarity
Active sitei136 – 1361Proton donor/acceptorBy similarity
Binding sitei137 – 1371SubstrateBy similarity
Binding sitei278 – 2781SubstrateBy similarity
Metal bindingi279 – 2791Calcium; via carbonyl oxygenBy similarity
Metal bindingi283 – 2831Calcium; via carbonyl oxygenBy similarity
Metal bindingi309 – 3091CalciumBy similarity
Metal bindingi329 – 3291Calcium; via carbonyl oxygenBy similarity
Binding sitei353 – 3531SubstrateBy similarity
Active sitei387 – 3871NucleophileBy 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. active induction of host immune response by virus Source: Reactome
  2. carbohydrate metabolic process Source: InterPro
  3. fusion of virus membrane with host plasma membrane Source: Reactome
  4. intracellular transport of viral protein in host cell Source: Reactome
  5. modulation by virus of host morphology or physiology Source: Reactome
  6. receptor-mediated endocytosis of virus by host cell Source: Reactome
  7. uncoating of virus Source: Reactome
  8. viral entry into host cell Source: Reactome
  9. viral genome packaging Source: Reactome
  10. viral life cycle Source: Reactome
  11. viral process Source: Reactome
  12. viral release from host cell Source: Reactome
  13. viral transcription Source: Reactome
  14. virion assembly Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_6145. Influenza Life Cycle.
REACT_6147. Entry of Influenza Virion into Host Cell via Endocytosis.
REACT_6212. Budding.
REACT_6213. Influenza Virus Induced Apoptosis.
REACT_6215. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
REACT_6235. Packaging of Eight RNA Segments.
REACT_6277. Assembly of Viral Components at the Budding Site.
REACT_6321. Uncoating of the Influenza Virion.
REACT_6326. Release.
REACT_6351. Fusion of the Influenza Virion to the Host Cell Endosome.
REACT_9491. Viral mRNA Translation.
SABIO-RKP03468.

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/Puerto Rico/8/1934 H1N1)
Taxonomic identifieri211044 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000009255: 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

GO - Cellular componenti

  1. endocytic vesicle membrane Source: Reactome
  2. endoplasmic reticulum membrane Source: Reactome
  3. endosome lumen Source: Reactome
  4. extracellular region Source: Reactome
  5. Golgi membrane Source: Reactome
  6. host cell plasma membrane Source: UniProtKB-KW
  7. integral component of membrane Source: UniProtKB-KW
  8. plasma membrane Source: Reactome
  9. 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 – 454454NeuraminidasePRO_0000078712Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi44 – 441N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi58 – 581N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi73 – 731N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi77 ↔ 402By similarity
Disulfide bondi109 ↔ 114By similarity
Glycosylationi131 – 1311N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi169 ↔ 216By similarity
Disulfide bondi218 ↔ 223By similarity
Glycosylationi220 – 2201N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi264 ↔ 277By similarity
Disulfide bondi266 ↔ 275By similarity
Disulfide bondi303 ↔ 320By similarity
Disulfide bondi406 ↔ 431By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Protein-protein interaction databases

IntActiP03468. 6 interactions.

Structurei

3D structure databases

ProteinModelPortaliP03468.
SMRiP03468. Positions 68-452.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66IntravirionSequence Analysis
Topological domaini36 – 454419Virion surfaceSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei7 – 3529Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft associationBy similarityAdd
BLAST
Regioni36 – 7540Hypervariable stalk regionAdd
BLAST
Regioni76 – 454379Head of neuraminidaseAdd
BLAST
Regioni262 – 2632Substrate 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.

P03468 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSICLVVGLI SLILQIGNII SIWISHSIQT GSQNHTGICN
60 70 80 90 100
QNIITYKNST WVKDTTSVIL TGNSSLCPIR GWAIYSKDNS IRIGSKGDVF
110 120 130 140 150
VIREPFISCS HLECRTFFLT QGALLNDKHS NGTVKDRSPY RALMSCPVGE
160 170 180 190 200
APSPYNSRFE SVAWSASACH DGMGWLTIGI SGPDNGAVAV LKYNGIITET
210 220 230 240 250
IKSWRKKILR TQESECACVN GSCFTIMTDG PSDGLASYKI FKIEKGKVTK
260 270 280 290 300
SIELNAPNSH YEECSCYPDT GKVMCVCRDN WHGSNRPWVS FDQNLDYQIG
310 320 330 340 350
YICSGVFGDN PRPEDGTGSC GPVYVDGANG VKGFSYRYGN GVWIGRTKSH
360 370 380 390 400
SSRHGFEMIW DPNGWTETDS KFSVRQDVVA MTDWSGYSGS FVQHPELTGL
410 420 430 440 450
DCMRPCFWVE LIRGRPKEKT IWTSASSISF CGVNSDTVDW SWPDGAELPF

SIDK
Length:454
Mass (Da):50,121
Last modified:March 6, 2007 - v2
Checksum:i7C52E0A9FD93A98B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti8 – 81I → T in AAM75160. (PubMed:11779399)Curated
Sequence conflicti51 – 511Q → H in AAA43415. (PubMed:6927853)Curated
Sequence conflicti128 – 1281K → R in AAA43412. (PubMed:7010182)Curated
Sequence conflicti131 – 1311N → S in ABO21711. (PubMed:15163504)Curated
Sequence conflicti131 – 1311N → S in ABD77678. 1 PublicationCurated
Sequence conflicti314 – 3141E → K in AAA43412. (PubMed:7010182)Curated
Sequence conflicti403 – 4031M → I in AAA43412. (PubMed:7010182)Curated
Sequence conflicti451 – 4511S → T in AAA43412. (PubMed:7010182)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02146 Genomic RNA. Translation: AAA43412.1.
AF389120 Genomic RNA. Translation: AAM75160.1.
EF467823 Genomic RNA. Translation: ABO21711.1.
CY009446 Genomic RNA. Translation: ABD77678.1.
K01031 Genomic RNA. Translation: AAA43415.1.
RefSeqiNP_040981.1. NC_002018.1.

Genome annotation databases

GeneIDi956530.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02146 Genomic RNA. Translation: AAA43412.1 .
AF389120 Genomic RNA. Translation: AAM75160.1 .
EF467823 Genomic RNA. Translation: ABO21711.1 .
CY009446 Genomic RNA. Translation: ABD77678.1 .
K01031 Genomic RNA. Translation: AAA43415.1 .
RefSeqi NP_040981.1. NC_002018.1.

3D structure databases

ProteinModelPortali P03468.
SMRi P03468. Positions 68-452.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P03468. 6 interactions.

Chemistry

BindingDBi P03468.
ChEMBLi CHEMBL2051.

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 956530.

Enzyme and pathway databases

Reactomei REACT_6145. Influenza Life Cycle.
REACT_6147. Entry of Influenza Virion into Host Cell via Endocytosis.
REACT_6212. Budding.
REACT_6213. Influenza Virus Induced Apoptosis.
REACT_6215. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
REACT_6235. Packaging of Eight RNA Segments.
REACT_6277. Assembly of Viral Components at the Budding Site.
REACT_6321. Uncoating of the Influenza Virion.
REACT_6326. Release.
REACT_6351. Fusion of the Influenza Virion to the Host Cell Endosome.
REACT_9491. Viral mRNA Translation.
SABIO-RK P03468.

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. "Structure of the neuraminidase gene in human influenza virus A/PR/8/34."
    Fields S., Winter G., Brownlee G.G.
    Nature 290:213-217(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments."
    de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M.
    Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
  4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  5. "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 1-71.
  6. "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.
  7. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  8. "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_I34A1
AccessioniPrimary (citable) accession number: P03468
Secondary accession number(s): A4GXH6
, Q20N35, Q84043, Q8JUU4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 6, 2007
Last modified: October 29, 2014
This is version 111 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, Reference 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