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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.1 Publication

Cofactori

Ca2+4 PublicationsNote: Binds 1 Ca(2+) ion per subunit.4 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. Inhibited by difluorosialic acid derivatives. Resistance to neuraminidase inhibitors is quite rare.1 Publication

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 oxygen4 Publications
Metal bindingi299 – 2991Calcium; via carbonyl oxygen4 Publications
Metal bindingi326 – 3261Calcium4 Publications
Metal bindingi348 – 3481Calcium; via carbonyl oxygen4 Publications
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 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. 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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66IntravirionSequence Analysis
Transmembranei7 – 3529Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini36 – 470435Virion surfaceSequence AnalysisAdd
BLAST

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

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 hostSequence Analysis
Glycosylationi66 – 661N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi87 – 871N-linked (GlcNAc...); by host3 Publications
Disulfide bondi93 ↔ 419
Disulfide bondi125 ↔ 130
Glycosylationi147 – 1471N-linked (GlcNAc...); by host3 Publications
Disulfide bondi177 ↔ 195
Disulfide bondi185 ↔ 232
Glycosylationi202 – 2021N-linked (GlcNAc...); by host3 Publications
Disulfide bondi234 ↔ 239
Disulfide bondi280 ↔ 293
Disulfide bondi282 ↔ 291
Disulfide bondi320 ↔ 338
Disulfide bondi423 ↔ 449

Post-translational modificationi

N-glycosylated.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.4 Publications

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03472.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft associationBy 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).By 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.

P03472-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNPNQKILCT SATALVIGTI AVLIGITNLG LNIGLHLKPS CNCSHSQPEA
60 70 80 90 100
TNASQTIINN YYNDTNITQI SNTNIQVEER AIRDFNNLTK GLCTINSWHI
110 120 130 140 150
YGKDNAVRIG EDSDVLVTRE PYVSCDPDEC RFYALSQGTT IRGKHSNGTI
160 170 180 190 200
HDRSQYRALI SWPLSSPPTV YNSRVECIGW SSTSCHDGKT RMSICISGPN
210 220 230 240 250
NNASAVIWYN RRPVTEINTW ARNILRTQES ECVCHNGVCP VVFTDGSATG
260 270 280 290 300
PAETRIYYFK EGKILKWEPL AGTAKHIEEC SCYGERAEIT CTCRDNWQGS
310 320 330 340 350
NRPVIRIDPV AMTHTSQYIC SPVLTDNPRP NDPTVGKCND PYPGNNNNGV
360 370 380 390 400
KGFSYLDGVN TWLGRTISIA SRSGYEMLKV PNALTDDKSK PTQGQTIVLN
410 420 430 440 450
TDWSGYSGSF MDYWAEGECY RACFYVELIR GRPKEDKVWW TSNSIVSMCS
460 470
STEFLGQWDW PDGAKIEYFL
Length:470
Mass (Da):52,469
Last modified:July 21, 1986 - v1
Checksum:iF114226CF93E1370
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti377 – 3771M → I in AAA43574. (PubMed:3660585)Curated
Sequence conflicti387 – 3882DK → ER in AAA43574. (PubMed:3660585)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11445 Genomic RNA. Translation: AAA43353.1.
M17813 Genomic RNA. Translation: AAA43574.1.
PIRiA00884. NMIV9.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11445 Genomic RNA. Translation: AAA43353.1 .
M17813 Genomic RNA. Translation: AAA43574.1 .
PIRi A00884. NMIV9.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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. 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: November 26, 2014
This is version 122 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