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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Tokyo/3/1967 H2N2)
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.UniRule annotation

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.

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.UniRule annotation

Cofactori

Protein has several cofactor binding sites:

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.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei118SubstrateUniRule annotation1
Active sitei151Proton donor/acceptorUniRule annotation1
Binding sitei152SubstrateUniRule annotation1
Binding sitei292SubstrateUniRule annotation1
Metal bindingi293Calcium; via carbonyl oxygenUniRule annotation3 Publications1
Metal bindingi297Calcium; via carbonyl oxygenUniRule annotation3 Publications1
Metal bindingi324CalciumUniRule annotation3 Publications1
Metal bindingi345Calcium; via carbonyl oxygenUniRule annotation3 Publications1
Metal bindingi346Calcium; via carbonyl oxygenUniRule annotation3 Publications1
Metal bindingi347Calcium; via carbonyl oxygen3 Publications1
Binding sitei371SubstrateUniRule annotation1
Active sitei406NucleophileUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGlycosidase, Hydrolase
LigandCalcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.2.1.18. 7479.
SABIO-RKiP06820.

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Names & Taxonomyi

Protein namesi
Recommended name:
NeuraminidaseUniRule annotation (EC:3.2.1.18UniRule annotation)
Gene namesi
Name:NAUniRule annotation
OrganismiInfluenza A virus (strain A/Tokyo/3/1967 H2N2)
Taxonomic identifieri380960 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]

Subcellular locationi

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

  • 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.UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 9IntravirionUniRule annotation9
Transmembranei10 – 30HelicalUniRule annotationAdd BLAST21
Topological domaini31 – 469Virion surfaceUniRule annotationAdd BLAST439

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechi

Chemistry databases

DrugBankiDB02829. 4-(Acetylamino)-3-[(Aminoacetyl)Amino]Benzoic Acid.
DB04565. 4-(Acetylamino)-3-[(Hydroxyacetyl)Amino]Benzoic Acid.
DB02268. 4-(Acetylamino)-3-Amino Benzoic Acid.
DB08570. 4-(ACETYLAMINO)-3-HYDROXY-5-NITROBENZOIC ACID.
DB08571. 4-(ACETYLAMINO)-5-AMINO-3-HYDROXYBENZOIC ACID.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000787201 – 469NeuraminidaseAdd BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi61N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi69N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi70N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi86N-linked (GlcNAc...) asparagine; by hostUniRule annotation3 Publications1
Disulfide bondi92 ↔ 417UniRule annotation
Disulfide bondi124 ↔ 129UniRule annotation
Glycosylationi146N-linked (GlcNAc...) asparagine; by host3 Publications1
Disulfide bondi175 ↔ 193
Disulfide bondi183 ↔ 230UniRule annotation
Glycosylationi200N-linked (GlcNAc...) asparagine; by host3 Publications1
Disulfide bondi232 ↔ 237UniRule annotation
Glycosylationi234N-linked (GlcNAc...) asparagine; by hostUniRule annotation2 Publications1
Disulfide bondi278 ↔ 291UniRule annotation
Disulfide bondi280 ↔ 289UniRule annotation
Disulfide bondi318 ↔ 337UniRule annotation
Glycosylationi402N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi421 ↔ 447UniRule annotation

Post-translational modificationi

N-glycosylated.UniRule annotation3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.UniRule annotation3 Publications

Chemistry databases

BindingDBiP06820.

Structurei

Secondary structure

1469
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi96 – 102Combined sources7
Helixi105 – 108Combined sources4
Turni109 – 111Combined sources3
Beta strandi121 – 124Combined sources4
Beta strandi129 – 132Combined sources4
Beta strandi137 – 139Combined sources3
Turni144 – 149Combined sources6
Beta strandi157 – 162Combined sources6
Beta strandi172 – 176Combined sources5
Beta strandi178 – 184Combined sources7
Beta strandi186 – 196Combined sources11
Beta strandi198 – 207Combined sources10
Beta strandi210 – 216Combined sources7
Beta strandi218 – 221Combined sources4
Beta strandi227 – 229Combined sources3
Beta strandi231 – 233Combined sources3
Beta strandi236 – 244Combined sources9
Beta strandi246 – 248Combined sources3
Beta strandi250 – 267Combined sources18
Beta strandi276 – 281Combined sources6
Beta strandi284 – 292Combined sources9
Beta strandi294 – 296Combined sources3
Beta strandi301 – 305Combined sources5
Turni307 – 309Combined sources3
Beta strandi312 – 316Combined sources5
Beta strandi319 – 321Combined sources3
Beta strandi324 – 326Combined sources3
Beta strandi330 – 332Combined sources3
Beta strandi337 – 339Combined sources3
Beta strandi353 – 356Combined sources4
Beta strandi359 – 366Combined sources8
Beta strandi368 – 371Combined sources4
Beta strandi374 – 381Combined sources8
Turni382 – 384Combined sources3
Beta strandi385 – 387Combined sources3
Beta strandi390 – 393Combined sources4
Beta strandi407 – 413Combined sources7
Beta strandi415 – 429Combined sources15
Turni430 – 432Combined sources3
Beta strandi435 – 437Combined sources3
Beta strandi439 – 451Combined sources13
Turni464 – 466Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1INGX-ray2.40A/B82-469[»]
1INHX-ray2.40A/B82-469[»]
1INWX-ray2.40A82-469[»]
1INXX-ray2.40A82-469[»]
1IVCX-ray2.40A/B82-469[»]
1IVDX-ray1.90A/B82-469[»]
1IVEX-ray2.40A/B82-469[»]
1IVFX-ray2.40A/B82-469[»]
1IVGX-ray1.90A/B82-469[»]
1NN2X-ray2.20A82-469[»]
2BATX-ray2.00A82-469[»]
ProteinModelPortaliP06820.
SMRiP06820.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06820.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationUniRule annotationAdd BLAST23
Regioni36 – 88Hypervariable stalk regionUniRule annotationAdd BLAST53
Regioni91 – 469Head of neuraminidaseUniRule annotationAdd BLAST379
Regioni276 – 277Substrate bindingUniRule annotation2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi179 – 182Poly-Ser4

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.UniRule annotation

Sequence similaritiesi

Belongs to the glycosyl hydrolase 34 family.UniRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Family and domain databases

CDDicd15483. Influenza_NA. 1 hit.
HAMAPiMF_04071. INFV_NRAM. 1 hit.
InterProiView protein in InterPro
IPR001860. Glyco_hydro_34.
IPR033654. Sialidase_Influenza_A/B.
IPR011040. Sialidases.
PfamiView protein in Pfam
PF00064. Neur. 1 hit.
SUPFAMiSSF50939. SSF50939. 1 hit.

Sequencei

Sequence statusi: Complete.

P06820-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSVSLTIATV CFLMQIAILV TTVTLHFKQH ECDSPASNQV
60 70 80 90 100
MPCEPIIIER NITEIVYLNN TTIEKEICPK VVEYRNWSKP QCQITGFAPF
110 120 130 140 150
SKDNSIRLSA GGDIWVTREP YVSCDPVKCY QFALGQGTTL DNKHSNDTVH
160 170 180 190 200
DRIPHRTLLM NELGVPFHLG TRQVCIAWSS SSCHDGKAWL HVCITGDDKN
210 220 230 240 250
ATASFIYDGR LVDSIGSWSQ NILRTQESEC VCINGTCTVV MTDGSASGRA
260 270 280 290 300
DTRILFIEEG KIVHISPLAG SAQHVEECSC YPRYPGVRCI CRDNWKGSNR
310 320 330 340 350
PVVDINMEDY SIDSSYVCSG LVGDTPRNDD RSSNSNCRNP NNERGTQGVK
360 370 380 390 400
GWAFDNGNDL WMGRTISKDL RSGYETFKVI GGWSTPNSKS QINRQVIVDS
410 420 430 440 450
DNRSGYSGIF SVEGKSCINR CFYVELIRGR KQETRVWWTS NSIVVFCGTS
460
GTYGTGSWPD GANINFMPI
Length:469
Mass (Da):52,131
Last modified:October 1, 1996 - v2
Checksum:iDF9F74BFFA3FEBC9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41E → D in AAO46245 (PubMed:15380362).1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K01393 Genomic RNA. Translation: AAB05621.1.
AY209929 Genomic RNA. Translation: AAO46245.1.

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.

Entry informationi

Entry nameiNRAM_I67A0
AccessioniPrimary (citable) accession number: P06820
Secondary accession number(s): Q6XUB0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: October 1, 1996
Last modified: June 7, 2017
This is version 127 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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