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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
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 (By similarity).By similarity
Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious.By similarity

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+1 PublicationNote: Binds 1 Ca2+ ion per subunit.1 Publication

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 sitei118Substrate1
Active sitei151Proton donor/acceptorBy similarity1
Binding sitei152Substrate1
Binding sitei293Substrate1
Metal bindingi294Calcium; via carbonyl oxygen1 Publication1
Metal bindingi298Calcium; via carbonyl oxygen1 Publication1
Metal bindingi324Calcium1 Publication1
Metal bindingi344Calcium; via carbonyl oxygen1 Publication1
Binding sitei368Substrate1
Active sitei402NucleophileBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.2.1.18. 7479.
SABIO-RKQ9IGQ6.

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/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
Taxonomic identifieri88776 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000008430 Componenti: Genome

Subcellular locationi

  • Virion membrane
  • Host apical cell membrane; Single-pass type II membrane protein

  • 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 – 27HelicalSequence analysisAdd BLAST21
Topological domaini28 – 469Virion surfaceSequence analysisAdd BLAST442

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1795169.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003105691 – 469NeuraminidaseAdd BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi88N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi92 ↔ 4171 Publication
Disulfide bondi124 ↔ 1291 Publication
Glycosylationi146N-linked (GlcNAc...); by host1 Publication1
Disulfide bondi184 ↔ 2311 Publication
Disulfide bondi233 ↔ 2381 Publication
Glycosylationi235N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi279 ↔ 2921 Publication
Disulfide bondi281 ↔ 2901 Publication
Disulfide bondi318 ↔ 3351 Publication
Disulfide bondi421 ↔ 4461 Publication

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiQ9IGQ6.

Interactioni

Subunit structurei

Homotetramer.1 Publication

Chemistry databases

BindingDBiQ9IGQ6.

Structurei

Secondary structure

1469
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi95 – 102Combined sources8
Helixi105 – 109Combined sources5
Beta strandi115 – 124Combined sources10
Beta strandi129 – 142Combined sources14
Helixi143 – 145Combined sources3
Turni146 – 149Combined sources4
Beta strandi157 – 162Combined sources6
Turni169 – 171Combined sources3
Beta strandi173 – 177Combined sources5
Beta strandi179 – 185Combined sources7
Beta strandi190 – 197Combined sources8
Beta strandi203 – 208Combined sources6
Beta strandi211 – 217Combined sources7
Beta strandi219 – 222Combined sources4
Beta strandi228 – 230Combined sources3
Beta strandi232 – 234Combined sources3
Beta strandi237 – 245Combined sources9
Beta strandi247 – 249Combined sources3
Beta strandi252 – 259Combined sources8
Beta strandi262 – 268Combined sources7
Beta strandi277 – 284Combined sources8
Beta strandi287 – 293Combined sources7
Beta strandi302 – 306Combined sources5
Beta strandi312 – 316Combined sources5
Beta strandi324 – 326Combined sources3
Beta strandi350 – 353Combined sources4
Beta strandi356 – 361Combined sources6
Beta strandi365 – 376Combined sources12
Turni377 – 381Combined sources5
Beta strandi388 – 399Combined sources12
Beta strandi403 – 408Combined sources6
Helixi410 – 413Combined sources4
Beta strandi416 – 429Combined sources14
Turni430 – 432Combined sources3
Beta strandi433 – 436Combined sources4
Beta strandi438 – 450Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3B7EX-ray1.45A/B83-467[»]
3BEQX-ray1.64A/B83-467[»]
3CYEX-ray1.65A/B83-469[»]
ProteinModelPortaliQ9IGQ6.
SMRiQ9IGQ6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9IGQ6.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationBy similarityAdd BLAST23
Regioni36 – 90Hypervariable stalk regionBy similarityAdd BLAST55
Regioni91 – 469Head of neuraminidaseBy similarityAdd BLAST379
Regioni277 – 278Substrate bindingBy similarity2

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.

Q9IGQ6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSICMVVGII SLILQIGNII SIWVSHSIQT GNQNHPETCN
60 70 80 90 100
QSIITYENNT WVNQTYVNIS NTNVVAGQDA TSVILTGNSS LCPISGWAIY
110 120 130 140 150
SKDNGIRIGS KGDVFVIREP FISCSHLECR TFFLTQGALL NDKHSNGTVK
160 170 180 190 200
DRSPYRTLMS CPVGEAPSPY NSRFESVAWS ASACHDGMGW LTIGISGPDN
210 220 230 240 250
GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT IMTDGPSNGQ
260 270 280 290 300
ASYKILKIEK GKVTKSIELN APNYHYEECS CYPDTGKVMC VCRDNWHGSN
310 320 330 340 350
RPWVSFDQNL DYQIGYICSG VFGDNPRPND GTGSCGPVSS NGANGIKGFS
360 370 380 390 400
FRYDNGVWIG RTKSTSSRSG FEMIWDPNGW TETDSSFSVR QDIVAITDWS
410 420 430 440 450
GYSGSFVQHP ELTGLDCMRP CFWVELIRGQ PKENTIWTSG SSISFCGVNS
460
DTVGWSWPDG AELPFSIDK
Length:469
Mass (Da):51,406
Last modified:October 1, 2000 - v1
Checksum:i28888692D4394159
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF250356 mRNA. Translation: AAF77036.1.
U94893 Genomic DNA. Translation: AAC57065.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF250356 mRNA. Translation: AAF77036.1.
U94893 Genomic DNA. Translation: AAC57065.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3B7EX-ray1.45A/B83-467[»]
3BEQX-ray1.64A/B83-467[»]
3CYEX-ray1.65A/B83-469[»]
ProteinModelPortaliQ9IGQ6.
SMRiQ9IGQ6.
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

BindingDBiQ9IGQ6.
ChEMBLiCHEMBL1795169.

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Proteomic databases

PRIDEiQ9IGQ6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

BRENDAi3.2.1.18. 7479.
SABIO-RKQ9IGQ6.

Miscellaneous databases

EvolutionaryTraceiQ9IGQ6.

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_I18A0
AccessioniPrimary (citable) accession number: Q9IGQ6
Secondary accession number(s): O10421
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 87 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.
South Carolina isolate has been sequenced from formalid fixed-lung tissues of a 21-year-old male which died in 1918 at Ft. Jackson, SC. Brevig Mission isolate has been sequenced from lung tissues of an Inuit woman buried in the permafrost in a gravesite near Brevig Mission, Alaska. This sample was recovered by John Hultin, retired pathologist.

Keywords - Technical termi

3D-structure, Complete proteome

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.