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Gene Review

NEU4  -  sialidase 4

Homo sapiens

Synonyms: LP5125, N-acetyl-alpha-neuraminidase 4, Sialidase-4
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Disease relevance of NEU4


High impact information on NEU4

  • In this study we describe a novel lysosomal lumen sialidase encoded by the NEU4 gene on human chromosome 2 [1].
  • In contrast to Neu1, Neu4 is targeted to lysosomes by the mannose 6-phosphate receptor and does not require association with other proteins for enzymatic activity [1].
  • Expression of Neu4 in the cells of sialidosis and galactosialidosis patients results in clearance of storage materials from lysosomes suggesting that Neu4 may be useful for developing new therapies for these conditions [1].
  • We demonstrate that Neu4 is ubiquitously expressed in human tissues and has broad substrate specificity by being active against sialylated oligosaccharides, glycoproteins, and gangliosides [1].
  • The NEU4 gene, identified by searching sequence databases for entries showing homologies to the human cytosolic sialidase NEU2, maps in 2q37 and encodes a 484-residue protein [3].

Biological context of NEU4

  • The siRNA-mediated NEU4 targeting, on the other hand, caused a significant inhibition of apoptosis and promotion of invasion and motility [2].
  • In cultured human colon cancer cells, the enzyme was up-regulated in the early stage of apoptosis induced by either the death ligand TRAIL or serum-depletion, and transfection of NEU4 resulted in acceleration of apoptosis and in decreased invasion and motility [2].

Anatomical context of NEU4


Analytical, diagnostic and therapeutic context of NEU4

  • Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family [3].
  • Lectin blot analyses revealed that desialylated forms of nearly 100 kDa glycoproteins were prominently increased with PNA in NEU4 transfectants, whereas only slight changes in glycolipids were detected as assessed by thin layer chromatography [2].


  1. Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells. Seyrantepe, V., Landry, K., Trudel, S., Hassan, J.A., Morales, C.R., Pshezhetsky, A.V. J. Biol. Chem. (2004) [Pubmed]
  2. Down-regulation of sialidase NEU4 may contribute to invasive properties of human colon cancers. Yamanami, H., Shiozaki, K., Wada, T., Yamaguchi, K., Uemura, T., Kakugawa, Y., Hujiya, T., Miyagi, T. Cancer Sci. (2007) [Pubmed]
  3. Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family. Monti, E., Bassi, M.T., Bresciani, R., Civini, S., Croci, G.L., Papini, N., Riboni, M., Zanchetti, G., Ballabio, A., Preti, A., Tettamanti, G., Venerando, B., Borsani, G. Genomics (2004) [Pubmed]
  4. Evidence for mitochondrial localization of a novel human sialidase (NEU4). Yamaguchi, K., Hata, K., Koseki, K., Shiozaki, K., Akita, H., Wada, T., Moriya, S., Miyagi, T. Biochem. J. (2005) [Pubmed]
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