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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)
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.1 Publication

Cofactori

Ca2+4 PublicationsNote: Binds 1 Ca2+ ion per subunit.4 Publications

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. Inhibited by difluorosialic acid derivatives. Resistance to neuraminidase inhibitors is quite rare.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei119Substrate1
Active sitei152Proton donor/acceptor1
Binding sitei153Substrate1
Binding sitei294Substrate1
Metal bindingi295Calcium; via carbonyl oxygen4 Publications1
Metal bindingi299Calcium; via carbonyl oxygen4 Publications1
Metal bindingi326Calcium4 Publications1
Metal bindingi348Calcium; via carbonyl oxygen4 Publications1
Binding sitei372Substrate1
Active sitei406Nucleophile1

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/Tern/Australia/G70C/1975 H11N9)
Taxonomic identifieri384509 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]

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_00000787211 – 470NeuraminidaseAdd BLAST470

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi63N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi66N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi87N-linked (GlcNAc...); by host3 Publications1
Disulfide bondi93 ↔ 419
Disulfide bondi125 ↔ 130
Glycosylationi147N-linked (GlcNAc...); by host3 Publications1
Disulfide bondi177 ↔ 195
Disulfide bondi185 ↔ 232
Glycosylationi202N-linked (GlcNAc...); by host3 Publications1
Disulfide bondi234 ↔ 239
Disulfide bondi280 ↔ 293
Disulfide bondi282 ↔ 291
Disulfide bondi320 ↔ 338
Disulfide bondi423 ↔ 449

Post-translational modificationi

N-glycosylated.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.4 Publications

Chemistry databases

BindingDBiP03472.

Structurei

Secondary structure

1470
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi96 – 103Combined sources8
Helixi106 – 110Combined sources5
Beta strandi115 – 126Combined sources12
Beta strandi129 – 143Combined sources15
Helixi144 – 146Combined sources3
Turni147 – 150Combined sources4
Beta strandi158 – 163Combined sources6
Turni170 – 172Combined sources3
Beta strandi174 – 186Combined sources13
Beta strandi188 – 198Combined sources11
Beta strandi200 – 202Combined sources3
Beta strandi204 – 209Combined sources6
Beta strandi212 – 218Combined sources7
Beta strandi220 – 223Combined sources4
Beta strandi225 – 227Combined sources3
Beta strandi229 – 231Combined sources3
Beta strandi238 – 246Combined sources9
Beta strandi248 – 250Combined sources3
Beta strandi252 – 260Combined sources9
Beta strandi263 – 269Combined sources7
Beta strandi278 – 285Combined sources8
Beta strandi288 – 294Combined sources7
Beta strandi296 – 298Combined sources3
Beta strandi303 – 308Combined sources6
Turni309 – 312Combined sources4
Beta strandi313 – 318Combined sources6
Beta strandi321 – 323Combined sources3
Beta strandi326 – 328Combined sources3
Beta strandi338 – 340Combined sources3
Helixi358 – 360Combined sources3
Beta strandi362 – 365Combined sources4
Beta strandi369 – 379Combined sources11
Turni381 – 385Combined sources5
Beta strandi392 – 403Combined sources12
Beta strandi407 – 410Combined sources4
Beta strandi416 – 420Combined sources5
Beta strandi423 – 431Combined sources9
Turni432 – 434Combined 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
1A14X-ray2.50N83-470[»]
1BJIX-ray2.00A83-470[»]
1F8BX-ray1.80A83-470[»]
1F8CX-ray1.70A83-470[»]
1F8DX-ray1.40A83-470[»]
1F8EX-ray1.40A83-470[»]
1INYX-ray2.40A83-470[»]
1L7FX-ray1.80A83-470[»]
1L7GX-ray1.85A83-470[»]
1L7HX-ray1.85A83-470[»]
1MWEX-ray1.70A83-470[»]
1NCAX-ray2.50N82-470[»]
1NCBX-ray2.50N82-470[»]
1NCCX-ray2.50N82-470[»]
1NMCX-ray2.50A/N83-470[»]
1NNAX-ray2.50A84-470[»]
1NNBX-ray2.80A84-470[»]
1NNCX-ray1.80A83-470[»]
1XOEX-ray2.20A84-470[»]
1XOGX-ray2.80A84-470[»]
2C4AX-ray2.15A83-470[»]
2C4LX-ray2.15A83-470[»]
2QWAX-ray1.70A83-470[»]
2QWBX-ray2.00A83-470[»]
2QWCX-ray1.60A83-470[»]
2QWDX-ray2.00A83-470[»]
2QWEX-ray2.00A83-470[»]
2QWFX-ray1.90A83-470[»]
2QWGX-ray1.80A83-470[»]
2QWHX-ray1.80A83-470[»]
2QWIX-ray2.00A83-470[»]
2QWJX-ray2.00A83-470[»]
2QWKX-ray1.80A83-470[»]
3NN9X-ray2.30A83-470[»]
3W09X-ray2.00A83-470[»]
4DGRX-ray1.55A82-470[»]
4NN9X-ray2.30A83-470[»]
4WEGX-ray2.10A83-470[»]
5NN9X-ray2.30A83-470[»]
6NN9X-ray2.30A83-470[»]
7NN9X-ray2.00A83-470[»]
ProteinModelPortaliP03472.
SMRiP03472.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03472.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationBy similarityAdd BLAST23
Regioni36 – 91Hypervariable stalk regionAdd BLAST56
Regioni92 – 470Head of neuraminidaseAdd BLAST379
Regioni278 – 279Substrate binding2

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.

P03472-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKILCT SATALVIGTI AVLIGITNLG LNIGLHLKPS CNCSHSQPEA
60 70 80 90 100
TNASQTIINN YYNDTNITQI SNTNIQVEER AIRDFNNLTK GLCTINSWHI
110 120 130 140 150
YGKDNAVRIG EDSDVLVTRE PYVSCDPDEC RFYALSQGTT IRGKHSNGTI
160 170 180 190 200
HDRSQYRALI SWPLSSPPTV YNSRVECIGW SSTSCHDGKT RMSICISGPN
210 220 230 240 250
NNASAVIWYN RRPVTEINTW ARNILRTQES ECVCHNGVCP VVFTDGSATG
260 270 280 290 300
PAETRIYYFK EGKILKWEPL AGTAKHIEEC SCYGERAEIT CTCRDNWQGS
310 320 330 340 350
NRPVIRIDPV AMTHTSQYIC SPVLTDNPRP NDPTVGKCND PYPGNNNNGV
360 370 380 390 400
KGFSYLDGVN TWLGRTISIA SRSGYEMLKV PNALTDDKSK PTQGQTIVLN
410 420 430 440 450
TDWSGYSGSF MDYWAEGECY RACFYVELIR GRPKEDKVWW TSNSIVSMCS
460 470
STEFLGQWDW PDGAKIEYFL
Length:470
Mass (Da):52,469
Last modified:July 21, 1986 - v1
Checksum:iF114226CF93E1370
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti377M → I in AAA43574 (PubMed:3660585).Curated1
Sequence conflicti387 – 388DK → ER in AAA43574 (PubMed:3660585).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11445 Genomic RNA. Translation: AAA43353.1.
M17813 Genomic RNA. Translation: AAA43574.1.
PIRiA00884. NMIV9.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11445 Genomic RNA. Translation: AAA43353.1.
M17813 Genomic RNA. Translation: AAA43574.1.
PIRiA00884. NMIV9.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A14X-ray2.50N83-470[»]
1BJIX-ray2.00A83-470[»]
1F8BX-ray1.80A83-470[»]
1F8CX-ray1.70A83-470[»]
1F8DX-ray1.40A83-470[»]
1F8EX-ray1.40A83-470[»]
1INYX-ray2.40A83-470[»]
1L7FX-ray1.80A83-470[»]
1L7GX-ray1.85A83-470[»]
1L7HX-ray1.85A83-470[»]
1MWEX-ray1.70A83-470[»]
1NCAX-ray2.50N82-470[»]
1NCBX-ray2.50N82-470[»]
1NCCX-ray2.50N82-470[»]
1NMCX-ray2.50A/N83-470[»]
1NNAX-ray2.50A84-470[»]
1NNBX-ray2.80A84-470[»]
1NNCX-ray1.80A83-470[»]
1XOEX-ray2.20A84-470[»]
1XOGX-ray2.80A84-470[»]
2C4AX-ray2.15A83-470[»]
2C4LX-ray2.15A83-470[»]
2QWAX-ray1.70A83-470[»]
2QWBX-ray2.00A83-470[»]
2QWCX-ray1.60A83-470[»]
2QWDX-ray2.00A83-470[»]
2QWEX-ray2.00A83-470[»]
2QWFX-ray1.90A83-470[»]
2QWGX-ray1.80A83-470[»]
2QWHX-ray1.80A83-470[»]
2QWIX-ray2.00A83-470[»]
2QWJX-ray2.00A83-470[»]
2QWKX-ray1.80A83-470[»]
3NN9X-ray2.30A83-470[»]
3W09X-ray2.00A83-470[»]
4DGRX-ray1.55A82-470[»]
4NN9X-ray2.30A83-470[»]
4WEGX-ray2.10A83-470[»]
5NN9X-ray2.30A83-470[»]
6NN9X-ray2.30A83-470[»]
7NN9X-ray2.00A83-470[»]
ProteinModelPortaliP03472.
SMRiP03472.
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

BindingDBiP03472.

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP03472.

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_I75A5
AccessioniPrimary (citable) accession number: P03472
Secondary accession number(s): Q84070
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 2, 2016
This is version 133 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.