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Q07577

- NRAM_I88A4

UniProt

Q07577 - NRAM_I88A4

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Protein

Neuraminidase

Gene
NA
Organism
Influenza A virus (strain A/Herring gull/DE/677/1988 H2N8)
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 sitei116 – 1161Substrate By similarity
Active sitei149 – 1491Proton donor/acceptor By similarity
Binding sitei150 – 1501Substrate By similarity
Binding sitei291 – 2911Substrate By similarity
Metal bindingi292 – 2921Calcium; via carbonyl oxygen By similarity
Metal bindingi296 – 2961Calcium; via carbonyl oxygen By similarity
Metal bindingi322 – 3221Calcium By similarity
Binding sitei368 – 3681Substrate By similarity
Active sitei402 – 4021Nucleophile 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/Herring gull/DE/677/1988 H2N8)
Taxonomic identifieri387243 [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 predictionAdd
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 – 470470NeuraminidasePRO_0000078695Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi46 – 461N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi54 – 541N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi84 – 841N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi90 ↔ 417 By similarity
Disulfide bondi122 ↔ 127 By similarity
Glycosylationi144 – 1441N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi182 ↔ 229 By similarity
Disulfide bondi231 ↔ 236 By similarity
Disulfide bondi277 ↔ 290 By similarity
Disulfide bondi279 ↔ 288 By similarity
Glycosylationi293 – 2931N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi316 ↔ 335 By similarity
Glycosylationi398 – 3981N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi421 ↔ 446 By similarity

Post-translational modificationi

N-glycosylated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ07577.
SMRiQ07577. Positions 82-467.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft association By similarityAdd
BLAST
Regioni39 – 8850Hypervariable stalk regionAdd
BLAST
Regioni89 – 470382Head of neuraminidaseAdd
BLAST
Regioni275 – 2762Substrate binding By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi439 – 4424Poly-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.

Q07577-1 [UniParc]FASTAAdd to Basket

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MNPNQKIITI GSVSLGLVVL NILLHIVSIT ITVLVLPGNG NNPSCNETVI    50
REYNETVRIE RVTQWHNTNV IEYLERPESD HFMNNTESLC DAKGFAPFSK 100
DNGIRIGSRG HVFVIREPFV SCSPTECRTF FLTQGSLLND KHSNGTVKDR 150
SPYRTLMSVQ IGQSPNVYQA RFEAVAWSAT ACHDGKKWMT IGVTGPDAKA 200
VAVVHYGGIP TDVINSWAGD ILRTQESSCT CIQGECYWVM TDGPANRQAQ 250
YRAFKAKQGK IIGQTEISFN GGHIEECSCY PNEGKVECVC RDNWTGTNRP 300
VLVISPDLSY RVGYLCAGLP SDTPRGEDSQ FTGSCTSPMG NQGYGVKGFG 350
FRQGNDVWMG RTISRTSRSG FEILKVRNGW VQNSKEQIKR QVVVDNLNWS 400
GYSGSFTLPV ELTKRNCLVP CFWVEMIRGK PEEKTIWTSS SSIVMCGVDH 450
EIADWSWHDG AILPFDIDKM 470
Length:470
Mass (Da):52,265
Last modified:February 1, 1995 - v1
Checksum:i28AF0B75E80539B7
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L06585 Genomic RNA. Translation: AAA43368.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L06585 Genomic RNA. Translation: AAA43368.1 .

3D structure databases

ProteinModelPortali Q07577.
SMRi Q07577. Positions 82-467.
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. "Phylogenetic analysis of the N8 neuraminidase gene of influenza A viruses."
    Saito T., Kawaoka Y., Webster R.G.
    Virology 193:868-876(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "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.
  3. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  4. "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_I88A4
AccessioniPrimary (citable) accession number: Q07577
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: September 3, 2014
This is version 88 of the entry and version 1 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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