Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Neuraminidase

Gene

NA

Organism
Influenza B virus (strain B/Lee/1940)
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 B 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 sitei116SubstrateUniRule annotation1
Active sitei149Proton donor/acceptorUniRule annotation1
Binding sitei150SubstrateUniRule annotation1
Binding sitei292SubstrateUniRule annotation1
Metal bindingi293Calcium; via carbonyl oxygenUniRule annotation2 Publications1
Metal bindingi297Calcium; via carbonyl oxygen2 Publications1
Metal bindingi324CalciumUniRule annotation2 Publications1
Metal bindingi346Calcium; via carbonyl oxygen2 Publications1
Binding sitei374SubstrateUniRule annotation1
Active sitei409NucleophileUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGlycosidase, Hydrolase
LigandCalcium, Metal-binding

Enzyme and pathway databases

SABIO-RKiP03474.

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 B virus (strain B/Lee/1940)
Taxonomic identifieri518987 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus B
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000119685 Componenti: Genome
  • UP000008158 Componenti: Genome

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 – 8IntravirionUniRule annotation8
Transmembranei9 – 31HelicalUniRule annotationAdd BLAST23
Topological domaini32 – 466Virion surfaceUniRule annotationAdd BLAST435

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi117E → G: Reduced substrate binding. 1 Publication1
Mutagenesisi149D → E: Almost complete loss of enzymatic activity. 1 Publication1
Mutagenesisi150R → K: Reduced substrate binding. 1 Publication1
Mutagenesisi223R → K: Reduced substrate binding. 1 Publication1
Mutagenesisi275E → D: Almost complete loss of enzymatic activity. 1 Publication1
Mutagenesisi374R → K: 80% loss of catalytic efficiency. 1 Publication1
Mutagenesisi374R → N: 94% loss of catalytic efficiency. 1 Publication1
Mutagenesisi409Y → F: Complete loss of enzymatic activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3377.
DrugBankiDB03342. 4-(Acetylamino)-3-Guanidinobenzoic Acid.
DB08570. 4-(ACETYLAMINO)-3-HYDROXY-5-NITROBENZOIC ACID.
DB07762. 4-(N-ACETYLAMINO)-3-[N-(2-ETHYLBUTANOYLAMINO)]BENZOIC ACID.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000787321 – 466NeuraminidaseAdd BLAST466

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi56N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi64N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi87 ↔ 420UniRule annotation
Disulfide bondi122 ↔ 127UniRule annotation
Glycosylationi144N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi182 ↔ 229UniRule annotation
Disulfide bondi231 ↔ 236UniRule annotation
Disulfide bondi277 ↔ 291UniRule annotation
Disulfide bondi279 ↔ 289UniRule annotation
Glycosylationi284N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi318 ↔ 337UniRule annotation
Disulfide bondi424 ↔ 447UniRule annotation

Post-translational modificationi

N-glycosylated.UniRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.UniRule annotation3 Publications

Chemistry databases

BindingDBiP03474.

Structurei

Secondary structure

1466
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi88 – 90Combined sources3
Beta strandi92 – 98Combined sources7
Helixi100 – 102Combined sources3
Beta strandi106 – 108Combined sources3
Beta strandi119 – 122Combined sources4
Beta strandi127 – 133Combined sources7
Beta strandi137 – 139Combined sources3
Turni144 – 147Combined sources4
Beta strandi155 – 160Combined sources6
Turni167 – 169Combined sources3
Beta strandi171 – 175Combined sources5
Beta strandi177 – 183Combined sources7
Beta strandi185 – 195Combined sources11
Turni197 – 199Combined sources3
Beta strandi201 – 206Combined sources6
Beta strandi209 – 215Combined sources7
Beta strandi217 – 220Combined sources4
Beta strandi226 – 228Combined sources3
Beta strandi230 – 232Combined sources3
Beta strandi235 – 241Combined sources7
Beta strandi245 – 247Combined sources3
Beta strandi251 – 257Combined sources7
Beta strandi260 – 265Combined sources6
Beta strandi268 – 270Combined sources3
Beta strandi275 – 292Combined sources18
Beta strandi294 – 296Combined sources3
Beta strandi301 – 306Combined sources6
Turni307 – 310Combined sources4
Beta strandi311 – 316Combined sources6
Beta strandi324 – 326Combined sources3
Beta strandi352 – 356Combined sources5
Beta strandi361 – 367Combined sources7
Beta strandi369 – 385Combined sources17
Turni387 – 389Combined sources3
Beta strandi395 – 406Combined sources12
Beta strandi410 – 416Combined sources7
Beta strandi418 – 432Combined sources15
Beta strandi435 – 437Combined sources3
Beta strandi439 – 448Combined sources10
Beta strandi450 – 452Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B9SX-ray2.50A77-466[»]
1B9TX-ray2.40A77-466[»]
1B9VX-ray2.35A77-466[»]
1INFX-ray2.40A77-466[»]
1INVX-ray2.40A77-466[»]
1IVBX-ray2.40A77-466[»]
1VCJX-ray2.40A78-466[»]
ProteinModelPortaliP03474.
SMRiP03474.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03474.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni13 – 35Involved in apical transport and lipid raft associationUniRule annotationAdd BLAST23
Regioni38 – 86Hypervariable stalk regionUniRule annotationAdd BLAST49
Regioni89 – 466Head of neuraminidaseUniRule annotationAdd BLAST378
Regioni275 – 276Substrate bindingUniRule annotation2

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

Phylogenomic databases

OrthoDBiVOG0900006X.

Family and domain databases

HAMAPiMF_04071. INFV_NRAM. 1 hit.
InterProiView protein in InterPro
IPR001860. Glyco_hydro_34.
IPR011040. Sialidases.
PfamiView protein in Pfam
PF00064. Neur. 1 hit.
SUPFAMiSSF50939. SSF50939. 1 hit.

Sequencei

Sequence statusi: Complete.

P03474-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLPSTVQTLT LLLTSGGVLL SLYVSASLSY LLYSDVLLKF SSTKTTAPTM
60 70 80 90 100
SLECTNASNA QTVNHSATKE MTFPPPEPEW TYPRLSCQGS TFQKALLISP
110 120 130 140 150
HRFGEIKGNS APLIIREPFV ACGPKECRHF ALTHYAAQPG GYYNGTRKDR
160 170 180 190 200
NKLRHLVSVK LGKIPTVENS IFHMAAWSGS ACHDGREWTY IGVDGPDNDA
210 220 230 240 250
LVKIKYGEAY TDTYHSYAHN ILRTQESACN CIGGDCYLMI TDGSASGISK
260 270 280 290 300
CRFLKIREGR IIKEILPTGR VEHTEECTCG FASNKTIECA CRDNSYTAKR
310 320 330 340 350
PFVKLNVETD TAEIRLMCTK TYLDTPRPDD GSIAGPCESN GDKWLGGIKG
360 370 380 390 400
GFVHQRMASK IGRWYSRTMS KTNRMGMELY VKYDGDPWTD SDALTLSGVM
410 420 430 440 450
VSIEEPGWYS FGFEIKDKKC DVPCIGIEMV HDGGKDTWHS AATAIYCLMG
460
SGQLLWDTVT GVDMAL
Length:466
Mass (Da):51,442
Last modified:July 21, 1986 - v1
Checksum:iE6FF3E634F132263
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02095 Genomic RNA. Translation: AAA43749.1.
PIRiA00886. NMIV4.
RefSeqiNP_056663.1. NC_002209.1.

Genome annotation databases

GeneIDi26824004.
KEGGivg:26824004.

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_INBLE
AccessioniPrimary (citable) accession number: P03474
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: June 7, 2017
This is version 128 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference 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