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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Whale/Maine/1/1984 H13N9)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Ca2+Note: Binds 1 Ca2+ ion per subunit.

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)DescriptionActionsGraphical viewLength
Binding sitei119SubstrateBy similarity1
Active sitei152Proton donor/acceptorBy similarity1
Binding sitei153SubstrateBy similarity1
Binding sitei294SubstrateBy similarity1
Metal bindingi295Calcium; via carbonyl oxygen1 Publication1
Metal bindingi299Calcium; via carbonyl oxygen1 Publication1
Metal bindingi326Calcium1 Publication1
Metal bindingi348Calcium; via carbonyl oxygen1 Publication1
Binding sitei372SubstrateBy similarity1
Active sitei406NucleophileBy similarity1

GO - Molecular functioni

GO - Biological processi

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/Whale/Maine/1/1984 H13N9)
Taxonomic identifieri11484 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6IntravirionSequence analysis6
Transmembranei7 – 35Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST29
Topological domaini36 – 470Virion surfaceSequence analysisAdd BLAST435

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000787251 – 470NeuraminidaseAdd BLAST470

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi42N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi52N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi63N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi66N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi87N-linked (GlcNAc...); by host2 Publications1
Disulfide bondi93 ↔ 4191 Publication
Disulfide bondi125 ↔ 1301 Publication
Glycosylationi147N-linked (GlcNAc...); by host1 Publication1
Disulfide bondi177 ↔ 1951 Publication
Disulfide bondi185 ↔ 2321 Publication
Glycosylationi202N-linked (GlcNAc...) (high mannose); by host1 Publication1
Disulfide bondi234 ↔ 2391 Publication
Disulfide bondi280 ↔ 2931 Publication
Disulfide bondi282 ↔ 2911 Publication
Disulfide bondi320 ↔ 3381 Publication
Disulfide bondi423 ↔ 4491 Publication

Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.2 Publications

Protein-protein interaction databases

MINTiMINT-1511103.

Structurei

Secondary structure

1470
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi96 – 104Combined sources9
Helixi106 – 110Combined sources5
Beta strandi122 – 126Combined sources5
Beta strandi129 – 135Combined sources7
Beta strandi138 – 143Combined sources6
Helixi144 – 146Combined sources3
Turni147 – 150Combined sources4
Beta strandi158 – 163Combined sources6
Turni170 – 172Combined sources3
Beta strandi174 – 186Combined sources13
Beta strandi191 – 198Combined sources8
Beta strandi204 – 218Combined sources15
Beta strandi220 – 223Combined sources4
Beta strandi229 – 231Combined sources3
Beta strandi238 – 246Combined sources9
Beta strandi248 – 250Combined sources3
Beta strandi252 – 260Combined sources9
Beta strandi263 – 269Combined sources7
Beta strandi281 – 285Combined sources5
Beta strandi288 – 292Combined sources5
Beta strandi296 – 298Combined sources3
Beta strandi303 – 308Combined sources6
Turni309 – 312Combined sources4
Beta strandi313 – 318Combined sources6
Beta strandi326 – 328Combined sources3
Beta strandi338 – 340Combined sources3
Beta strandi354 – 357Combined sources4
Helixi358 – 360Combined sources3
Beta strandi362 – 365Combined sources4
Beta strandi369 – 379Combined sources11
Turni381 – 385Combined sources5
Beta strandi392 – 403Combined sources12
Beta strandi407 – 410Combined sources4
Beta strandi415 – 420Combined sources6
Beta strandi423 – 431Combined sources9
Turni432 – 434Combined sources3
Beta strandi437 – 439Combined sources3
Beta strandi441 – 453Combined sources13
Helixi466 – 469Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NCDX-ray2.90N83-470[»]
1NMAX-ray3.00N83-470[»]
1NMBX-ray2.20N1-470[»]
2B8HX-ray2.20A/B/C/D83-470[»]
ProteinModelPortaliP05803.
SMRiP05803.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05803.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationBy similarityAdd BLAST23
Regioni36 – 89Hypervariable stalk regionAdd BLAST54
Regioni90 – 470Head of neuraminidaseAdd BLAST381
Regioni278 – 279Substrate bindingBy similarity2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi345 – 348Poly-Asn4

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

CDDicd15483. Influenza_NA. 1 hit.
Gene3Di2.120.10.10. 1 hit.
InterProiIPR001860. Glyco_hydro_34.
IPR033654. Sialidase_Influenza_A/B.
IPR011040. Sialidases.
[Graphical view]
PfamiPF00064. Neur. 1 hit.
[Graphical view]
SUPFAMiSSF50939. SSF50939. 1 hit.

Sequencei

Sequence statusi: Complete.

P05803-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKILCT SATALVIGTI AVLIGIVNLG LNIGLHLKPS CNCSRSQPEA
60 70 80 90 100
TNASQTIINN YYNETNITQI SNTNIQVEER ASREFNNLTK GLCTINSWHI
110 120 130 140 150
YGKDNAVRIG EDSDVLVTRE PYVSCDPDEC RFYALSQGTT IRGKHSNGTI
160 170 180 190 200
HDRSQYRDLI SWPLSSPPTV YNSRVECIGW SSTSCHDGRA RMSICISGPN
210 220 230 240 250
NNASAVIWYN RRPVTEINTW ARNILRTQES ECVCQNGVCP VVFTDGSATG
260 270 280 290 300
PAETRIYYFK EGKILKWEPL TGTAKHIEEC SCYGEQAGVT CTCRDNWQGS
310 320 330 340 350
NRPVIQIDPV AMTHTSQYIC SPVLTDNPRP NDPTVGKCND PYPGNNNNGV
360 370 380 390 400
KGFSYLDGGN TWLGRTISIA SRSGYEMLKV PNALTDDRSK PTQGQTIVLN
410 420 430 440 450
TDWSGYSGSF MDYWAEGECY RACFYVELIR GRPKEDKVWW TSNSIVSMCS
460 470
STEFLGQWNW PDGAKIEYFL
Length:470
Mass (Da):52,394
Last modified:November 1, 1988 - v1
Checksum:iF2054DD47BBAB996
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17812 Genomic RNA. Translation: AAA43575.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17812 Genomic RNA. Translation: AAA43575.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NCDX-ray2.90N83-470[»]
1NMAX-ray3.00N83-470[»]
1NMBX-ray2.20N1-470[»]
2B8HX-ray2.20A/B/C/D83-470[»]
ProteinModelPortaliP05803.
SMRiP05803.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1511103.

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP05803.
PROiP05803.

Family and domain databases

CDDicd15483. Influenza_NA. 1 hit.
Gene3Di2.120.10.10. 1 hit.
InterProiIPR001860. Glyco_hydro_34.
IPR033654. Sialidase_Influenza_A/B.
IPR011040. Sialidases.
[Graphical view]
PfamiPF00064. Neur. 1 hit.
[Graphical view]
SUPFAMiSSF50939. SSF50939. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNRAM_I84A1
AccessioniPrimary (citable) accession number: P05803
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: November 2, 2016
This is version 123 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.

Keywords - Technical termi

3D-structure

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.