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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 – 1101Substrate By similarity
Active sitei143 – 1431Proton donor/acceptor By similarity
Binding sitei144 – 1441Substrate By similarity
Binding sitei285 – 2851Substrate By similarity
Metal bindingi286 – 2861Calcium; via carbonyl oxygen By similarity
Metal bindingi290 – 2901Calcium; via carbonyl oxygen By similarity
Metal bindingi316 – 3161Calcium By similarity
Binding sitei365 – 3651Substrate By similarity
Active sitei399 – 3991Nucleophile By 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; 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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66Intravirion Reviewed prediction
Transmembranei7 – 3529Helical; Signal-anchor for type II membrane protein; Reviewed prediction
Add
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 468468Neuraminidase
PRO_0000078716Add
BLAST

Amino acid modifications

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

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft association By similarity
Add
BLAST
Regioni36 – 8247Hypervariable stalk region
Add
BLAST
Regioni83 – 468386Head of neuraminidase
Add
BLAST
Regioni269 – 2702Substrate binding By 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.

Sequence similaritiesi

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

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MNPNQKIITI GSASLGLVIF NILLHVASIT LGIISVTKDN KVHICNTTEV    50
YNETVRVETV VIPVNNTIYL NHEPEFLNNT EPLCDVSGFA IVSKDNGIRI 100
GSRGHIFVIR EPFVSCGPSE CRTFFLTQGA LLNDKHSNNT VKDRSPYRAL 150
MSVPLGSSPN AYQAKFESVG WSATACHDGK KWMAIGVSGA DDDAYAVIHY 200
GGVPTDVIRS WRKQILRTQE SSCVCIKGEC YWVMTDGPAN NQASYKIFKS 250
QKGMVVDEKE ISFQGGHIEE CSCYPNMGKV ECVCRDNWNG MNRPILIFDE 300
KLEYEVGYLC AGIPTDTPRV QDSSFTGSCT NAVGRSGTNN YGVKGFGFRQ 350
GNSVWAGRTI SVSSRSGFEV LLIEDGWIRP SKTISKKVEV LNNKNWSGYS 400
GAFTIPTAMT SKNCIVPCFW LEMIRGKPEE RTSIWTSSSS TVFCGVSSEV 450
PGWSWDDGAI LPFDIDKM 468
Length:468
Mass (Da):51,590
Last modified:February 1, 1991 - v2
Checksum:i58A235445B2D3F1F
GO

Sequence conflict

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

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: September 3, 2014
This is version 100 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

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