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P03469

- NRAM_I77AB

UniProt

P03469 - NRAM_I77AB

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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/USSR/90/1977 H1N1)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi

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.By similarity

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 sitei118 – 1181SubstrateBy similarity
Active sitei151 – 1511Proton donor/acceptorBy similarity
Binding sitei152 – 1521SubstrateBy similarity
Binding sitei293 – 2931SubstrateBy similarity
Metal bindingi294 – 2941Calcium; via carbonyl oxygenBy similarity
Metal bindingi298 – 2981Calcium; via carbonyl oxygenBy similarity
Metal bindingi324 – 3241CalciumBy similarity
Binding sitei368 – 3681SubstrateBy similarity
Active sitei402 – 4021NucleophileBy 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-RKP03469.

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/USSR/90/1977 H1N1)
Taxonomic identifieri381516 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000007793: 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. 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

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_0000078723Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi44 – 441N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi58 – 581N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi63 – 631N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi68 – 681N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi88 – 881N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi92 ↔ 417By similarity
Disulfide bondi124 ↔ 129By similarity
Glycosylationi146 – 1461N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi184 ↔ 231By similarity
Disulfide bondi233 ↔ 238By similarity
Glycosylationi235 – 2351N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi279 ↔ 292By similarity
Disulfide bondi281 ↔ 290By similarity
Disulfide bondi318 ↔ 335By similarity
Glycosylationi365 – 3651N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi421 ↔ 447By similarity
Glycosylationi455 – 4551N-linked (GlcNAc...); by hostSequence Analysis

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

3D structure databases

ProteinModelPortaliP03469.
SMRiP03469. Positions 85-468.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66IntravirionSequence Analysis
Topological domaini36 – 470435Virion 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
Regioni11 – 3323Involved in apical transport and lipid raft associationBy similarityAdd
BLAST
Regioni36 – 9055Hypervariable stalk regionAdd
BLAST
Regioni91 – 470380Head of neuraminidaseAdd
BLAST
Regioni277 – 2782Substrate bindingBy similarity

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.

P03469-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSICMAIGII SLILQIGNII SIWVSHSIQT GSQNHTGICN
60 70 80 90 100
QRIITYENST WVNQTYVNIS NTNVVAGKDT TSMTLAGNSS LCPIRGWAIY
110 120 130 140 150
SKDNSIRIGS KGDVFVIREP FISCSHLECR TFFLTQGALL NDKHSNGTVK
160 170 180 190 200
DRSPYRALMS CPIGEAPSPY NSRFESVAWS ASACHDGMGW LTIGISGPDD
210 220 230 240 250
GAVAVLKYNG IITETIKSWR KQILRTQESE CVCVNGSCFT IMTDGPSDGP
260 270 280 290 300
ASYRIFKIEK GKITKSIELD APNSHYEECS CYPDTGTVMC VCRDNWHGSN
310 320 330 340 350
RPWVSFNQNL DYQIGYICSG VFGDNPRPKD GKGSCDPVNV DGADGVKGFS
360 370 380 390 400
YRYGNGVWIG RTKSNSSRKG FEMIWDPNGW TDTDSNFLVK QDVVAMTDWS
410 420 430 440 450
GYSGSFVQHP ELTGLDCMRP CFWVELIRGR PREKTTIWTS GSSISFCGVN
460 470
SDTVNWSWPD GAELPFTIDK
Length:470
Mass (Da):51,863
Last modified:March 6, 2007 - v2
Checksum:iE3578AC6519D0266
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti48 – 481I → T in AAA43420. (PubMed:7080440)Curated
Sequence conflicti48 – 481I → T in AAA43447. (PubMed:6927853)Curated
Sequence conflicti51 – 511Q → H in AAA43420. (PubMed:7080440)Curated
Sequence conflicti51 – 511Q → H in AAA43447. (PubMed:6927853)Curated
Sequence conflicti185 – 1851H → Y in AAA43449. (PubMed:6708174)Curated
Sequence conflicti190 – 1901W → C in AAA43449. (PubMed:6708174)Curated
Sequence conflicti334 – 3341S → R in AAA43449. (PubMed:6708174)Curated
Sequence conflicti357 – 3571V → G in AAA43449. (PubMed:6708174)Curated
Sequence conflicti383 – 3831T → P in AAA43449. (PubMed:6708174)Curated
Sequence conflicti393 – 3931V → I in AAA43449. (PubMed:6708174)Curated
Sequence conflicti405 – 4051S → R in AAA43449. (PubMed:6708174)Curated
Sequence conflicti461 – 4611G → D in AAA43449. (PubMed:6708174)Curated
Sequence conflicti466 – 4661F → L in AAA43449. (PubMed:6708174)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K02018 Genomic RNA. Translation: AAA43449.1.
CY010374 Genomic RNA. Translation: ABD95353.1.
DQ508899 Genomic RNA. Translation: ABF21333.1.
J02564 Genomic RNA. Translation: AAA43420.1.
K01038 Genomic RNA. Translation: AAA43447.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K02018 Genomic RNA. Translation: AAA43449.1 .
CY010374 Genomic RNA. Translation: ABD95353.1 .
DQ508899 Genomic RNA. Translation: ABF21333.1 .
J02564 Genomic RNA. Translation: AAA43420.1 .
K01038 Genomic RNA. Translation: AAA43447.1 .

3D structure databases

ProteinModelPortali P03469.
SMRi P03469. Positions 85-468.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Enzyme and pathway databases

SABIO-RK P03469.

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. "Nucleotide sequence of the influenza virus A/USSR/90/77 neuraminidase gene."
    Concannon P., Kwolek C.J., Salser W.A.
    J. Virol. 50:654-656(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Complete genome sequencing and analysis of selected influenza virus vaccine strains spanning six decades (1933-1999)."
    Mbawuike I.N., Zhang Y., Yamada R.E., Nino D., Bui H.-H., Sette A., Couch R.B.
    Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  4. "Block deletions in the neuraminidase genes from some influenza A viruses of the N1 subtype."
    Blok J., Air G.M.
    Virology 118:229-234(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 41-86.
  5. "Sequence variation at the 3' end of the neuraminidase gene from 39 influenza type A viruses."
    Blok J., Air G.M.
    Virology 121:211-229(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-86.
  6. "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.
  7. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  8. "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.

Entry informationi

Entry nameiNRAM_I77AB
AccessioniPrimary (citable) accession number: P03469
Secondary accession number(s): Q1WP06, Q83958, Q83959
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 6, 2007
Last modified: October 29, 2014
This is version 101 of the entry and version 2 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

Complete proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3