Neuraminidase

Details

Name
Neuraminidase
Synonyms
  • 3.2.1.18
Gene Name
NA
Organism
Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9)
Amino acid sequence
>lcl|BSEQ0011188|Neuraminidase
MNPNQKILCTSATALVIGTIAVLIGITNLGLNIGLHLKPSCNCSHSQPEATNASQTIINN
YYNDTNITQISNTNIQVEERAIRDFNNLTKGLCTINSWHIYGKDNAVRIGEDSDVLVTRE
PYVSCDPDECRFYALSQGTTIRGKHSNGTIHDRSQYRALISWPLSSPPTVYNSRVECIGW
SSTSCHDGKTRMSICISGPNNNASAVIWYNRRPVTEINTWARNILRTQESECVCHNGVCP
VVFTDGSATGPAETRIYYFKEGKILKWEPLAGTAKHIEECSCYGERAEITCTCRDNWQGS
NRPVIRIDPVAMTHTSQYICSPVLTDNPRPNDPTVGKCNDPYPGNNNNGVKGFSYLDGVN
TWLGRTISIASRSGYEMLKVPNALTDDKSKPTQGQTIVLNTDWSGYSGSFMDYWAEGECY
RACFYVELIRGRPKEDKVWWTSNSIVSMCSSTEFLGQWDWPDGAKIEYFL
Number of residues
470
Molecular Weight
52468.405
Theoretical pI
6.57
GO Classification
Functions
exo-alpha-(2->3)-sialidase activity / exo-alpha-(2->6)-sialidase activity / exo-alpha-(2->8)-sialidase activity / metal ion binding
Processes
carbohydrate metabolic process
Components
host cell plasma membrane / integral component of membrane / virion membrane
General Function
Metal ion binding
Specific Function
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.
Pfam Domain Function
Transmembrane Regions
7-35
Cellular Location
Virion membrane
Gene sequence
>lcl|BSEQ0003306|1413 bp
ATGAATCCAAATCAGAAGATTCTATGCACTTCTGCCACTGCTCTCGTAATAGGCACAATT
GCAGTACTCATAGGAATAACGAACTTAGGATTGAACATAGGACTACATCTGAAACCGAGC
TGCAATTGCTCACACTCACAACCCGAAGCAACCAATGCAAGCCAAACAATAATAAATAAC
TATTATAATGACACAAACATCACCCAGATAAGTAATACCAACATTCAGGTAGAGGAAAGG
GCAATTAGAGATTTCAATAACTTGACCAAAGGGCTCTGTACTATAAATTCATGGCACATA
TATGGGAAAGACAATGCGGTGAGAATTGGGGAGGACTCAGATGTTTTAGTCACAAGAGAA
CCCTATGTCTCCTGTGACCCAGATGAGTGCAGGTTCTATGCTCTCAGCCAAGGGACAACA
ATCAGAGGAAAACACTCAAATGGAACAATACACGATAGGTCTCAATATCGTGCCCTGATA
AGCTGGCCATTGTCATCACCGCCCACAGTATACAACAGCAGAGTGGAATGCATTGGATGG
TCAAGTACTAGTTGTCATGATGGCAAAACCAGGATGTCAATATGCATATCAGGCCCGAAC
AATAACGCATCAGCAGTGATCTGGTACAATAGAAGGCCTGTGACAGAAATCAACACATGG
GCCCGAAACATACTAAGGACACAAGAATCTGAATGCGTATGCCACAACGGTGTCTGCCCG
GTAGTGTTCACAGATGGGTCTGCCACTGGACCTGCAGAAACAAGAATATACTATTTTAAA
GAAGGGAAGATCTTAAAATGGGAACCTCTGGCTGGAACTGCTAAGCATATCGAAGAATGC
TCATGCTACGGAGAGCGAGCAGAGATTACTTGCACGTGTAGGGATAATTGGCAAGGCTCA
AATAGACCAGTAATTCGGATAGATCCAGTGGCGATGACACATACTAGTCAGTATATATGT
AGCCCTGTTCTCACAGATAACCCCCGACCGAATGACCCAACTGTAGGTAAGTGTAACGAC
CCTTATCCAGGCAATAACAACAATGGGGTCAAAGGGTTTTCATATCTGGATGGAGTTAAT
ACTTGGCTAGGGAGGACAATAAGCATAGCTTCAAGATCCGGATATGAGATGCTAAAGGTG
CCAAATGCATTGACAGACGATAAGTCAAAGCCCACTCAAGGTCAGACAATCGTCTTAAAC
ACTGACTGGAGTGGTTACAGTGGGTCCTTCATGGACTATTGGGCTGAGGGGGAATGCTAC
CGAGCGTGTTTTTACGTGGAGTTAATACGTGGGAGACCTAAGGAGGATAAAGTGTGGTGG
ACCAGTAATAGTATAGTATCGATGTGTTCCAGCACAGAATTCCTTGGACAATGGGACTGG
CCTGATGGGGCTAAAATAGAGTACTTCCTCTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP03472
UniProtKB Entry NameNRAM_I75A5
GenBank Protein ID324416
GenBank Gene IDM11445
General References
  1. Air GM, Ritchie LR, Laver WG, Colman PM: Gene and protein sequence of an influenza neuraminidase with hemagglutinin activity. Virology. 1985 Aug;145(1):117-22. [Article]
  2. Air GM, Webster RG, Colman PM, Laver WG: Distribution of sequence differences in influenza N9 neuraminidase of tern and whale viruses and crystallization of the whale neuraminidase complexed with antibodies. Virology. 1987 Oct;160(2):346-54. [Article]
  3. Nayak DP, Hui EK, Barman S: Assembly and budding of influenza virus. Virus Res. 2004 Dec;106(2):147-65. [Article]
  4. Moscona A: Neuraminidase inhibitors for influenza. N Engl J Med. 2005 Sep 29;353(13):1363-73. [Article]
  5. Suzuki Y: Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses. Biol Pharm Bull. 2005 Mar;28(3):399-408. [Article]
  6. Baker AT, Varghese JN, Laver WG, Air GM, Colman PM: Three-dimensional structure of neuraminidase of subtype N9 from an avian influenza virus. Proteins. 1987;2(2):111-7. [Article]
  7. Bossart-Whitaker P, Carson M, Babu YS, Smith CD, Laver WG, Air GM: Three-dimensional structure of influenza A N9 neuraminidase and its complex with the inhibitor 2-deoxy 2,3-dehydro-N-acetyl neuraminic acid. J Mol Biol. 1993 Aug 20;232(4):1069-83. [Article]
  8. Varghese JN, Epa VC, Colman PM: Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase. Protein Sci. 1995 Jun;4(6):1081-7. [Article]
  9. Varghese JN, Colman PM, van Donkelaar A, Blick TJ, Sahasrabudhe A, McKimm-Breschkin JL: Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11808-12. [Article]
  10. Kim JH, Resende R, Wennekes T, Chen HM, Bance N, Buchini S, Watts AG, Pilling P, Streltsov VA, Petric M, Liggins R, Barrett S, McKimm-Breschkin JL, Niikura M, Withers SG: Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity. Science. 2013 Apr 5;340(6128):71-5. doi: 10.1126/science.1232552. Epub 2013 Feb 21. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02529(2R,4S,5R,6R)-5-Acetamido-4-amino-6-(diethylcarbamoyl)oxane-2-carboxylic acidexperimentalunknownDetails
DB02600Oseltamivir acidexperimentalunknownDetails
DB032575-[1-(Acetylamino)-3-Methylbutyl]-2,5-Anhydro-3,4-Dideoxy-4-(Methoxycarbonyl)Pentonic AcidexperimentalunknownDetails
DB03321Des(carbamimidoyl) zanamivirexperimentalunknownDetails
DB034202,4-deoxy-4-guanidino-5-N-acetyl-neuraminic acidexperimentalunknownDetails
DB035034-Acetyl-4-guanidino-6-methyl(propyl)carboxamide-4,5-dihydro-2H-pyran-2-carboxylic acidexperimentalunknownDetails
DB06614Peramivirapproved, investigationalunknownDetails
DB03721N-acetyl-alpha-neuraminic acidexperimentalunknownDetails
DB039912-deoxy-2,3-dehydro-N-acetylneuraminic acidexperimentalunknownDetails
DB042279-Amino-2-deoxy-2,3-dehydro-n-acetyl-neuraminic acidexperimentalunknownDetails