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Q6DPK2

- NRAM_I02A1

UniProt

Q6DPK2 - NRAM_I02A1

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Protein
Neuraminidase
Gene
NA
Organism
Influenza A virus (strain A/Guinea fowl/Hong Kong/38/2002 H5N1 genotype X0)
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 sitei98 – 981Substrate By similarity
Active sitei131 – 1311Proton donor/acceptor By similarity
Binding sitei132 – 1321Substrate By similarity
Binding sitei273 – 2731Substrate By similarity
Metal bindingi274 – 2741Calcium; via carbonyl oxygen By similarity
Metal bindingi278 – 2781Calcium; via carbonyl oxygen By similarity
Metal bindingi304 – 3041Calcium By similarity
Binding sitei348 – 3481Substrate 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
Complete GO annotation...

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/Guinea fowl/Hong Kong/38/2002 H5N1 genotype X0)
Taxonomic identifieri284208 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Felis catus (Cat) (Felis silvestris catus) [TaxID: 9685]
Homo sapiens (Human) [TaxID: 9606]
Panthera pardus (Leopard) (Felis pardus) [TaxID: 9691]
Panthera tigris (Tiger) [TaxID: 9694]
Sus scrofa (Pig) [TaxID: 9823]

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 – 2721Helical; Reviewed prediction
Add
BLAST
Topological domaini28 – ›358›331Virion 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 – ›358›358Neuraminidase
PRO_0000310934Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi68 – 681N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi104 ↔ 109 By similarity
Glycosylationi126 – 1261N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi164 ↔ 211 By similarity
Disulfide bondi213 ↔ 218 By similarity
Glycosylationi215 – 2151N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi259 ↔ 272 By similarity
Disulfide bondi261 ↔ 270 By similarity
Disulfide bondi298 ↔ 315 By similarity

Post-translational modificationi

N-glycosylated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ6DPK2.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft association By similarity
Add
BLAST
Regioni36 – 7035Hypervariable stalk region By similarity
Add
BLAST
Regioni71 – ›358›288Head of neuraminidase By similarity
Add
BLAST
Regioni257 – 2582Substrate 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: Fragment.

Q6DPK2-1 [UniParc]FASTAAdd to Basket

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MNPNRKIITI GSICMVIGIV SLMLQIGNII SIWVSHSIQT ENQHQAEPIS    50
NTNFLTEKAV ASVTLAGNSS LCPISGWAIH SKDNGIRIGS KGDVFVIREP 100
FISCSHLECR TFFLTQGALL NDKHSNGTVK DRSPHRTLMS CPVGEAPSPY 150
NSRFESVAWS ASACHDGTSW LTIGISGPDN GAVAVLKYNG IITDTIKSWR 200
NNILRTQESE CACVNGSCFT VMTDGPSNGQ ASYKIFKMEK GKVVKSVELD 250
APNYHYEECS CYPDAGEVTC VCRDNWHGSN RPWVSFNQNL EYQIGYICSG 300
VFGDNPRPND GTGSCGPMSL NGAYGVKGFS FKYGNGVWIG RTKSTNSRSG 350
FEMIWDPN 358
Length:358
Mass (Da):39,066
Last modified:August 16, 2004 - v1
Checksum:i14EB44BF919407C6
GO

Non-terminal residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei358 – 3581

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY651457 Genomic RNA. Translation: AAT73339.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY651457 Genomic RNA. Translation: AAT73339.1 .

3D structure databases

ProteinModelPortali Q6DPK2.
ModBasei 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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Entry informationi

Entry nameiNRAM_I02A1
AccessioniPrimary (citable) accession number: Q6DPK2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: August 16, 2004
Last modified: September 3, 2014
This is version 58 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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