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P03474

- NRAM_INBLE

UniProt

P03474 - NRAM_INBLE

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Protein

Neuraminidase

Gene

NA

Organism
Influenza B virus (strain B/Lee/1940)
Status
Reviewed - 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 By similarity.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

Binds 1 calcium ion per subunit.3 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. Resistance to neuraminidase inhibitors is quite rare.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei116 – 1161SubstrateBy similarity
Active sitei149 – 1491Proton donor/acceptorBy similarity
Binding sitei150 – 1501SubstrateBy similarity
Binding sitei292 – 2921SubstrateBy similarity
Metal bindingi293 – 2931Calcium; via carbonyl oxygen2 Publications
Metal bindingi297 – 2971Calcium; via carbonyl oxygen2 Publications
Metal bindingi324 – 3241Calcium2 Publications
Metal bindingi346 – 3461Calcium; via carbonyl oxygen2 Publications
Binding sitei374 – 3741SubstrateBy similarity
Active sitei409 – 4091NucleophileBy similarity

GO - Molecular functioni

  1. exo-alpha-(2->3)-sialidase activity Source: UniProtKB-EC
  2. exo-alpha-(2->6)-sialidase activity Source: UniProtKB-EC
  3. exo-alpha-(2->8)-sialidase activity Source: UniProtKB-EC
  4. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. carbohydrate metabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

SABIO-RKP03474.

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 B virus (strain B/Lee/1940)
Taxonomic identifieri107412 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus B
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000008158: Genome

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. In the virion, forms a mushroom-shaped spike on the surface of the membrane By similarity.By similarity

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. virion membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi117 – 1171E → G: Reduced substrate binding. 1 Publication
Mutagenesisi149 – 1491D → E: Almost complete loss of enzymatic activity. 1 Publication
Mutagenesisi150 – 1501R → K: Reduced substrate binding. 1 Publication
Mutagenesisi223 – 2231R → K: Reduced substrate binding. 1 Publication
Mutagenesisi275 – 2751E → D: Almost complete loss of enzymatic activity. 1 Publication
Mutagenesisi374 – 3741R → K: 80% loss of catalytic efficiency. 1 Publication
Mutagenesisi374 – 3741R → N: 94% loss of catalytic efficiency. 1 Publication
Mutagenesisi409 – 4091Y → F: Complete loss of enzymatic activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 466466NeuraminidasePRO_0000078732Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi56 – 561N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi64 – 641N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi87 ↔ 420
Disulfide bondi122 ↔ 127
Glycosylationi144 – 1441N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi182 ↔ 229
Disulfide bondi231 ↔ 236
Disulfide bondi277 ↔ 291
Disulfide bondi279 ↔ 289
Glycosylationi284 – 2841N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi318 ↔ 337
Disulfide bondi424 ↔ 447

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.3 Publications

Structurei

Secondary structure

1
466
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi88 – 903
Beta strandi92 – 987
Helixi100 – 1023
Beta strandi106 – 1083
Beta strandi119 – 1224
Beta strandi127 – 1337
Beta strandi137 – 1393
Turni144 – 1474
Beta strandi155 – 1606
Turni167 – 1693
Beta strandi171 – 1755
Beta strandi177 – 1837
Beta strandi185 – 19511
Turni197 – 1993
Beta strandi201 – 2066
Beta strandi209 – 2157
Beta strandi217 – 2204
Beta strandi226 – 2283
Beta strandi230 – 2323
Beta strandi235 – 2417
Beta strandi245 – 2473
Beta strandi251 – 2577
Beta strandi260 – 2656
Beta strandi268 – 2703
Beta strandi275 – 29218
Beta strandi294 – 2963
Beta strandi301 – 3066
Turni307 – 3104
Beta strandi311 – 3166
Beta strandi324 – 3263
Beta strandi352 – 3565
Beta strandi361 – 3677
Beta strandi369 – 38517
Turni387 – 3893
Beta strandi395 – 40612
Beta strandi410 – 4167
Beta strandi418 – 43215
Beta strandi435 – 4373
Beta strandi439 – 44810
Beta strandi450 – 4523

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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. Positions 77-466.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03474.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66IntravirionSequence Analysis
Topological domaini36 – 466431Virion surfaceSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei7 – 3529Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni39 – 6931Hypervariable stalk regionAdd
BLAST
Regioni70 – 466397Head of neuraminidaseAdd
BLAST
Regioni275 – 2762Substrate bindingBy similarity

Sequence similaritiesi

Belongs to the glycosyl hydrolase 34 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di2.120.10.10. 1 hit.
InterProiIPR001860. Glyco_hydro_34.
IPR011040. Sialidases.
[Graphical view]
PfamiPF00064. Neur. 1 hit.
[Graphical view]
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:
EMBL
GenBank
DDBJ
Links Updated
J02095 Genomic RNA. Translation: AAA43749.1.
PIRiA00886. NMIV4.
RefSeqiNP_056663.1. NC_002209.1.

Genome annotation databases

GeneIDi956541.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J02095 Genomic RNA. Translation: AAA43749.1 .
PIRi A00886. NMIV4.
RefSeqi NP_056663.1. NC_002209.1.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1B9S X-ray 2.50 A 77-466 [» ]
1B9T X-ray 2.40 A 77-466 [» ]
1B9V X-ray 2.35 A 77-466 [» ]
1INF X-ray 2.40 A 77-466 [» ]
1INV X-ray 2.40 A 77-466 [» ]
1IVB X-ray 2.40 A 77-466 [» ]
1VCJ X-ray 2.40 A 78-466 [» ]
ProteinModelPortali P03474.
SMRi P03474. Positions 77-466.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P03474.
ChEMBLi CHEMBL3377.

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 956541.

Enzyme and pathway databases

SABIO-RK P03474.

Miscellaneous databases

EvolutionaryTracei P03474.

Family and domain databases

Gene3Di 2.120.10.10. 1 hit.
InterProi IPR001860. Glyco_hydro_34.
IPR011040. Sialidases.
[Graphical view ]
Pfami PF00064. Neur. 1 hit.
[Graphical view ]
SUPFAMi SSF50939. SSF50939. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "Complete nucleotide sequence of the neuraminidase gene of influenza B virus."
    Shaw M.W., Lamb R.A., Erickson B.W., Briedis D.J., Choppin P.W.
    Proc. Natl. Acad. Sci. U.S.A. 79:6817-6821(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Site-directed mutagenesis of catalytic residues of influenza virus neuraminidase as an aid to drug design."
    Ghate A.A., Air G.M.
    Eur. J. Biochem. 258:320-331(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLU-117; ASP-149; ARG-150; ARG-223; GLU-275; ARG-374 AND TYR-409.
  3. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  4. "Structures of aromatic inhibitors of influenza virus neuraminidase."
    Jedrzejas M.J., Singh S., Brouillette W.J., Laver W.G., Air G.M., Luo M.
    Biochemistry 34:3144-3151(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 77-466 IN COMPLEX WITH SYNTHETIC INHIBITOR AND CALCIUM, SUBUNIT, COFACTOR, GLYCOSYLATION AT ASN-284.
  5. "Novel aromatic inhibitors of influenza virus neuraminidase make selective interactions with conserved residues and water molecules in the active site."
    Finley J.B., Atigadda V.R., Duarte F., Zhao J.J., Brouillette W.J., Air G.M., Luo M.
    J. Mol. Biol. 293:1107-1119(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-466 IN COMPLEX WITH SYNTHETIC INHIBITOR AND CALCIUM, SUBUNIT, COFACTOR.
  6. "A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase."
    Lommer B.S., Ali S.M., Bajpai S.N., Brouillette W.J., Air G.M., Luo M.
    Acta Crystallogr. D 60:1017-1023(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 78-466 IN COMPLEX WITH SYNTHETIC INHIBITOR, SUBUNIT, COFACTOR.

Entry informationi

Entry nameiNRAM_INBLE
AccessioniPrimary (citable) accession number: P03474
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 29, 2014
This is version 108 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 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.

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

External Data

Dasty 3