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P03478

- NRAM_I72A5

UniProt

P03478 - NRAM_I72A5

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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Shearwater/Australia/1972 H6N5)
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 sitei110 – 1101SubstrateBy similarity
Active sitei143 – 1431Proton donor/acceptorBy similarity
Binding sitei144 – 1441SubstrateBy similarity
Binding sitei285 – 2851SubstrateBy similarity
Metal bindingi286 – 2861Calcium; via carbonyl oxygenBy similarity
Metal bindingi290 – 2901Calcium; via carbonyl oxygenBy similarity
Metal bindingi316 – 3161CalciumBy similarity
Binding sitei365 – 3651SubstrateBy similarity
Active sitei399 – 3991NucleophileBy 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/Shearwater/Australia/1972 H6N5)
Taxonomic identifieri383604 [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

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 – 468468NeuraminidasePRO_0000078716Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi46 – 461N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi52 – 521N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi65 – 651N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi78 – 781N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi84 ↔ 414By similarity
Disulfide bondi116 ↔ 121By similarity
Glycosylationi138 – 1381N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi176 ↔ 223By similarity
Disulfide bondi225 ↔ 230By similarity
Disulfide bondi271 ↔ 284By similarity
Disulfide bondi273 ↔ 282By similarity
Disulfide bondi310 ↔ 329By similarity
Glycosylationi395 – 3951N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi418 ↔ 444By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

3D structure databases

ProteinModelPortaliP03478.
SMRiP03478. Positions 76-465.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66IntravirionSequence Analysis

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 – 8247Hypervariable stalk regionAdd
BLAST
Regioni83 – 468386Head of neuraminidaseAdd
BLAST
Regioni269 – 2702Substrate bindingBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi437 – 4404Poly-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.

P03478-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSASLGLVIF NILLHVASIT LGIISVTKDN KVHICNTTEV
60 70 80 90 100
YNETVRVETV VIPVNNTIYL NHEPEFLNNT EPLCDVSGFA IVSKDNGIRI
110 120 130 140 150
GSRGHIFVIR EPFVSCGPSE CRTFFLTQGA LLNDKHSNNT VKDRSPYRAL
160 170 180 190 200
MSVPLGSSPN AYQAKFESVG WSATACHDGK KWMAIGVSGA DDDAYAVIHY
210 220 230 240 250
GGVPTDVIRS WRKQILRTQE SSCVCIKGEC YWVMTDGPAN NQASYKIFKS
260 270 280 290 300
QKGMVVDEKE ISFQGGHIEE CSCYPNMGKV ECVCRDNWNG MNRPILIFDE
310 320 330 340 350
KLEYEVGYLC AGIPTDTPRV QDSSFTGSCT NAVGRSGTNN YGVKGFGFRQ
360 370 380 390 400
GNSVWAGRTI SVSSRSGFEV LLIEDGWIRP SKTISKKVEV LNNKNWSGYS
410 420 430 440 450
GAFTIPTAMT SKNCIVPCFW LEMIRGKPEE RTSIWTSSSS TVFCGVSSEV
460
PGWSWDDGAI LPFDIDKM
Length:468
Mass (Da):51,590
Last modified:February 1, 1991 - v2
Checksum:i58A235445B2D3F1F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti26 – 261V → G in CAA24278. (PubMed:6896994)Curated
Sequence conflicti31 – 333LGI → WGT in CAA24278. (PubMed:6896994)Curated
Sequence conflicti50 – 501V → A in CAA24278. (PubMed:6896994)Curated
Sequence conflicti55 – 595VRVET → ARAEK in CAA24278. (PubMed:6896994)Curated
Sequence conflicti69 – 702YL → HS in CAA24278. (PubMed:6896994)Curated
Sequence conflicti84 – 841C → R in CAA24278. (PubMed:6896994)Curated
Sequence conflicti94 – 10714KDNGI…RGHIF → NGHGTRTGQEGTHS in CAA24278. (PubMed:6896994)CuratedAdd
BLAST
Sequence conflicti115 – 1151S → A in BAF36387. 1 PublicationCurated
Sequence conflicti335 – 3351R → G in BAF36387. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M24740 Genomic RNA. Translation: AAA43672.1.
AB278601 Genomic RNA. Translation: BAF36387.1.
V01094 Unassigned RNA. Translation: CAA24278.1.
PIRiA00890. NMIVN5.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M24740 Genomic RNA. Translation: AAA43672.1 .
AB278601 Genomic RNA. Translation: BAF36387.1 .
V01094 Unassigned RNA. Translation: CAA24278.1 .
PIRi A00890. NMIVN5.

3D structure databases

ProteinModelPortali P03478.
SMRi P03478. Positions 76-465.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

PROi P03478.

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. "Molecular cloning and analysis of the N5 neuraminidase subtype from an avian influenza virus."
    Harley V.R., Ward C.W., Hudson P.J.
    Virology 169:239-243(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "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 (NOV-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "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 1-107.
  4. "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.
  5. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  6. "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_I72A5
AccessioniPrimary (citable) accession number: P03478
Secondary accession number(s): A0A9J2, Q84104
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1991
Last modified: October 29, 2014
This is version 102 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