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P03472

- NRAM_I75A5

UniProt

P03472 - NRAM_I75A5

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Protein

Neuraminidase

Gene
NA
Organism
Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)
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. 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.

Cofactori

Binds 1 calcium ion per subunit.

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei119 – 1191Substrate
Active sitei152 – 1521Proton donor/acceptor
Binding sitei153 – 1531Substrate
Binding sitei294 – 2941Substrate
Metal bindingi295 – 2951Calcium; via carbonyl oxygen
Metal bindingi299 – 2991Calcium; via carbonyl oxygen
Metal bindingi326 – 3261Calcium
Metal bindingi348 – 3481Calcium; via carbonyl oxygen
Binding sitei372 – 3721Substrate
Active sitei406 – 4061Nucleophile

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

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 negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]

Subcellular locationi

Virion membrane By similarity. Host apical cell membrane; 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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66Intravirion Reviewed prediction
Transmembranei7 – 3529Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini36 – 470435Virion surface Reviewed predictionAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 470470NeuraminidasePRO_0000078721Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi63 – 631N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi66 – 661N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi87 – 871N-linked (GlcNAc...); by host
Disulfide bondi93 ↔ 419
Disulfide bondi125 ↔ 130
Glycosylationi147 – 1471N-linked (GlcNAc...); by host
Disulfide bondi177 ↔ 195
Disulfide bondi185 ↔ 232
Glycosylationi202 – 2021N-linked (GlcNAc...); by host
Disulfide bondi234 ↔ 239
Disulfide bondi280 ↔ 293
Disulfide bondi282 ↔ 291
Disulfide bondi320 ↔ 338
Disulfide bondi423 ↔ 449

Post-translational modificationi

N-glycosylated.

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.

Structurei

Secondary structure

1
470
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi96 – 1038
Helixi106 – 1105
Beta strandi115 – 12612
Beta strandi129 – 14315
Helixi144 – 1463
Turni147 – 1504
Beta strandi158 – 1636
Turni170 – 1723
Beta strandi174 – 18613
Beta strandi188 – 19811
Beta strandi200 – 2023
Beta strandi204 – 2096
Beta strandi212 – 2187
Beta strandi220 – 2234
Beta strandi225 – 2273
Beta strandi229 – 2313
Beta strandi238 – 2469
Beta strandi248 – 2503
Beta strandi252 – 2609
Beta strandi263 – 2697
Beta strandi278 – 2858
Beta strandi288 – 2947
Beta strandi296 – 2983
Beta strandi303 – 3086
Turni309 – 3124
Beta strandi313 – 3186
Beta strandi321 – 3233
Beta strandi326 – 3283
Beta strandi338 – 3403
Helixi358 – 3603
Beta strandi362 – 3654
Beta strandi369 – 37911
Turni381 – 3855
Beta strandi392 – 40312
Beta strandi407 – 4104
Beta strandi416 – 4205
Beta strandi423 – 4319
Turni432 – 4343
Beta strandi441 – 45313
Helixi466 – 4694

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
5NN9X-ray2.30A83-470[»]
6NN9X-ray2.30A83-470[»]
7NN9X-ray2.00A83-470[»]
ProteinModelPortaliP03472.
SMRiP03472. Positions 82-470.

Miscellaneous databases

EvolutionaryTraceiP03472.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft association By similarityAdd
BLAST
Regioni36 – 9156Hypervariable stalk regionAdd
BLAST
Regioni92 – 470379Head of neuraminidaseAdd
BLAST
Regioni278 – 2792Substrate binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi345 – 3484Poly-Asn

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.

Sequence similaritiesi

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.

P03472-1 [UniParc]FASTAAdd to Basket

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MNPNQKILCT SATALVIGTI AVLIGITNLG LNIGLHLKPS CNCSHSQPEA    50
TNASQTIINN YYNDTNITQI SNTNIQVEER AIRDFNNLTK GLCTINSWHI 100
YGKDNAVRIG EDSDVLVTRE PYVSCDPDEC RFYALSQGTT IRGKHSNGTI 150
HDRSQYRALI SWPLSSPPTV YNSRVECIGW SSTSCHDGKT RMSICISGPN 200
NNASAVIWYN RRPVTEINTW ARNILRTQES ECVCHNGVCP VVFTDGSATG 250
PAETRIYYFK EGKILKWEPL AGTAKHIEEC SCYGERAEIT CTCRDNWQGS 300
NRPVIRIDPV AMTHTSQYIC SPVLTDNPRP NDPTVGKCND PYPGNNNNGV 350
KGFSYLDGVN TWLGRTISIA SRSGYEMLKV PNALTDDKSK PTQGQTIVLN 400
TDWSGYSGSF MDYWAEGECY RACFYVELIR GRPKEDKVWW TSNSIVSMCS 450
STEFLGQWDW PDGAKIEYFL 470
Length:470
Mass (Da):52,469
Last modified:July 21, 1986 - v1
Checksum:iF114226CF93E1370
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti377 – 3771M → I in AAA43574. 1 Publication
Sequence conflicti387 – 3882DK → ER in AAA43574. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M11445 Genomic RNA. Translation: AAA43353.1.
M17813 Genomic RNA. Translation: AAA43574.1.
PIRiA00884. NMIV9.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M11445 Genomic RNA. Translation: AAA43353.1 .
M17813 Genomic RNA. Translation: AAA43574.1 .
PIRi A00884. NMIV9.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1A14 X-ray 2.50 N 83-470 [» ]
1BJI X-ray 2.00 A 83-470 [» ]
1F8B X-ray 1.80 A 83-470 [» ]
1F8C X-ray 1.70 A 83-470 [» ]
1F8D X-ray 1.40 A 83-470 [» ]
1F8E X-ray 1.40 A 83-470 [» ]
1INY X-ray 2.40 A 83-470 [» ]
1L7F X-ray 1.80 A 83-470 [» ]
1L7G X-ray 1.85 A 83-470 [» ]
1L7H X-ray 1.85 A 83-470 [» ]
1MWE X-ray 1.70 A 83-470 [» ]
1NCA X-ray 2.50 N 82-470 [» ]
1NCB X-ray 2.50 N 82-470 [» ]
1NCC X-ray 2.50 N 82-470 [» ]
1NMC X-ray 2.50 A/N 83-470 [» ]
1NNA X-ray 2.50 A 84-470 [» ]
1NNB X-ray 2.80 A 84-470 [» ]
1NNC X-ray 1.80 A 83-470 [» ]
1XOE X-ray 2.20 A 84-470 [» ]
1XOG X-ray 2.80 A 84-470 [» ]
2C4A X-ray 2.15 A 83-470 [» ]
2C4L X-ray 2.15 A 83-470 [» ]
2QWA X-ray 1.70 A 83-470 [» ]
2QWB X-ray 2.00 A 83-470 [» ]
2QWC X-ray 1.60 A 83-470 [» ]
2QWD X-ray 2.00 A 83-470 [» ]
2QWE X-ray 2.00 A 83-470 [» ]
2QWF X-ray 1.90 A 83-470 [» ]
2QWG X-ray 1.80 A 83-470 [» ]
2QWH X-ray 1.80 A 83-470 [» ]
2QWI X-ray 2.00 A 83-470 [» ]
2QWJ X-ray 2.00 A 83-470 [» ]
2QWK X-ray 1.80 A 83-470 [» ]
3NN9 X-ray 2.30 A 83-470 [» ]
3W09 X-ray 2.00 A 83-470 [» ]
4DGR X-ray 1.55 A 82-470 [» ]
4NN9 X-ray 2.30 A 83-470 [» ]
5NN9 X-ray 2.30 A 83-470 [» ]
6NN9 X-ray 2.30 A 83-470 [» ]
7NN9 X-ray 2.00 A 83-470 [» ]
ProteinModelPortali P03472.
SMRi P03472. Positions 82-470.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi P03472.

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P03472.

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. "Gene and protein sequence of an influenza neuraminidase with hemagglutinin activity."
    Air G.M., Ritchie L.R., Laver W.G., Colman P.M.
    Virology 145:117-122(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Distribution of sequence differences in influenza N9 neuraminidase of tern and whale viruses and crystallization of the whale neuraminidase complexed with antibodies."
    Air G.M., Webster R.G., Colman P.M., Laver W.G.
    Virology 160:346-354(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Assembly and budding of influenza virus."
    Nayak D.P., Hui E.K., Barman S.
    Virus Res. 106:147-165(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  4. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  5. "Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses."
    Suzuki Y.
    Biol. Pharm. Bull. 28:399-408(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  6. "Three-dimensional structure of neuraminidase of subtype N9 from an avian influenza virus."
    Baker A.T., Varghese J.N., Laver W.G., Air G.M., Colman P.M.
    Proteins 2:111-117(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 83-470.
  7. "Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid."
    Bossart-Whitaker P., Carson M., Babu Y.S., Smith C.D., Laver W.G., Air G.M.
    J. Mol. Biol. 232:1069-1083(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 83-470 IN COMPLEX WITH CALCIUM AND SUBSTRATE ANALOG, DISULFIDE BOND, ACTIVE SITE, COFACTOR, SUBUNIT.
  8. "Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase."
    Varghese J.N., Epa V.C., Colman P.M.
    Protein Sci. 4:1081-1087(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 83-470 IN COMPLEX WITH CALCIUM AND SUBSTRATE ANALOG, COFACTOR, DISULFIDE BOND, SUBUNIT, GLYCOSYLATION AT ASN-87; ASN-147 AND ASN-202.
  9. "Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases."
    Varghese J.N., Colman P.M., van Donkelaar A., Blick T.J., Sahasrabudhe A., McKimm-Breschkin J.L.
    Proc. Natl. Acad. Sci. U.S.A. 94:11808-11812(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 83-470 IN COMPLEX WITH CALCIUM, COFACTOR, ACTIVE SITE, DISULFIDE BOND, GLYCOSYLATION AT ASN-87; ASN-147 AND ASN-202.
  10. "Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity."
    Kim J.H., Resende R., Wennekes T., Chen H.M., Bance N., Buchini S., Watts A.G., Pilling P., Streltsov V.A., Petric M., Liggins R., Barrett S., McKimm-Breschkin J.L., Niikura M., Withers S.G.
    Science 340:71-75(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 83-470 IN COMPLEX WITH CALCIUM AND SUBSTRATE ANALOG, CATALYTIC ACTIVITY, ACTIVE SITE, IDENTIFICATION BY MASS SPECTROMETRY, COFACTOR, ENZYME REGULATION, DISULFIDE BOND, GLYCOSYLATION AT ASN-87; ASN-147 AND ASN-202.

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: September 3, 2014
This is version 119 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

External Data

Dasty 3

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