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P03477

- NRAM_I68A3

UniProt

P03477 - NRAM_I68A3

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Protein
Neuraminidase
Gene
NA
Organism
Influenza A virus (strain A/Turkey/Ontario/6118/1968 H8N4)
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 sitei117 – 1171Substrate By similarity
Active sitei150 – 1501Proton donor/acceptor By similarity
Binding sitei151 – 1511Substrate By similarity
Binding sitei292 – 2921Substrate By similarity
Metal bindingi293 – 2931Calcium; via carbonyl oxygen By similarity
Metal bindingi297 – 2971Calcium; via carbonyl oxygen By similarity
Metal bindingi323 – 3231Calcium By similarity
Binding sitei369 – 3691Substrate By similarity
Active sitei403 – 4031Nucleophile 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/Turkey/Ontario/6118/1968 H8N4)
Taxonomic identifieri311175 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
ProteomesiUP000007770: Genome

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
Topological domaini36 – 470435Virion surface 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 – 470470Neuraminidase
PRO_0000078718Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi91 ↔ 418 By similarity
Disulfide bondi123 ↔ 128 By similarity
Glycosylationi145 – 1451N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi183 ↔ 230 By similarity
Disulfide bondi232 ↔ 237 By similarity
Disulfide bondi278 ↔ 291 By similarity
Disulfide bondi280 ↔ 289 By similarity
Disulfide bondi317 ↔ 334 By similarity
Glycosylationi399 – 3991N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi422 ↔ 447 By similarity

Post-translational modificationi

N-glycosylated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer By similarity.

Structurei

3D structure databases

ProteinModelPortaliP03477.
SMRiP03477. Positions 81-468.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft association By similarity
Add
BLAST
Regioni36 – 8954Hypervariable stalk region By similarity
Add
BLAST
Regioni90 – 469380Head of neuraminidase By similarity
Add
BLAST
Regioni276 – 2772Substrate binding By 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.

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.

P03477-1 [UniParc]FASTAAdd to Basket

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MNPNQKIITI GSASIVLTTI GLLLQITSLC SIWFSHYNQV TQPHEQACSN    50
NTTNYYNETF VNVTNVQNNY TTIIEPSAPN VVHYSSGRDL CPVKGWAPLS 100
KDNGIRIGSR GEVFVIREPF ISCSISECRT FFLTQGALLN DKHSNGTVKD 150
RSPFRTLMSC PMGVAPSPSN SRFESVAWSA TACSDGPGWL TLGITGPDAT 200
AVAVLKYNGI ITDTLKSWKG NIMRTQESEC VCQDEFCYTL ITDGPSNAQA 250
FYKILKIRKG KIVSVKDVNA TGFHFEECSC YPSGTDVECV CRDNWRGSNR 300
PWIRFNSDLD YQIGYVCSGI FGDNPRPVDG IGSCNSPVNN GKGRYGVKGF 350
SFRYGDGVWI GRTKSLESRS GFEMVWDANG WVSTDKDSNG VQDIIDNNNW 400
SGYSGSFSIR WETTGRNCTV PCFWVEMIRG QPKEKTIWTS GSSIAFCGVN 450
SDTTGWSWPD GALLPFDIDK 470
Length:470
Mass (Da):51,891
Last modified:February 6, 2007 - v2
Checksum:iB9292CA549C98C30
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251Q → P in AAA43364. 1 Publication
Sequence conflicti25 – 251Q → P in CAA24277. 1 Publication
Sequence conflicti40 – 401V → G in AAA43364. 1 Publication
Sequence conflicti40 – 401V → G in CAA24277. 1 Publication
Sequence conflicti50 – 567NNTTNYY → TTQRITI in AAA43364. 1 Publication
Sequence conflicti50 – 567NNTTNYY → TTQRITI in CAA24277. 1 Publication
Sequence conflicti75 – 784EPSA → DPQP in AAA43364. 1 Publication
Sequence conflicti75 – 784EPSA → DPQP in CAA24277. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY207528 Genomic RNA. Translation: AAO62042.1.
CY014660 Genomic RNA. Translation: ABI84520.1.
AB289344 Genomic RNA. Translation: BAF43469.1.
K01013 Genomic RNA. Translation: AAA43364.1.
V01093 Genomic RNA. Translation: CAA24277.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY207528 Genomic RNA. Translation: AAO62042.1 .
CY014660 Genomic RNA. Translation: ABI84520.1 .
AB289344 Genomic RNA. Translation: BAF43469.1 .
K01013 Genomic RNA. Translation: AAA43364.1 .
V01093 Genomic RNA. Translation: CAA24277.1 .

3D structure databases

ProteinModelPortali P03477.
SMRi P03477. Positions 81-468.
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. "Genetic analysis of multiple N3, N4, and N6 influenza A virus neuraminidase genes."
    Webby R.J., Humberd J.L., Krauss S.L.
    Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Establishment of gene library of all haemagglutinin (HA) and neuraminidase (NA) subtypes for the control of influenza A virus infection."
    Tanaka Y., Kida H., Sakoda Y.
    Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  4. "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 1-79.
  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_I68A3
AccessioniPrimary (citable) accession number: P03477
Secondary accession number(s): Q6XV48
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 6, 2007
Last modified: September 3, 2014
This is version 91 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

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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