The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NEU3  -  sialidase 3 (membrane sialidase)

Homo sapiens

Synonyms: Ganglioside sialidase, Membrane sialidase, N-acetyl-alpha-neuraminidase 3, Sialidase-3
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NEU3

  • Here we demonstrate that mice overexpressing the human ortholog (NEU3) develop diabetic phenotype by 18-22 weeks associated with hyperinsulinemia, islet hyperplasia, and increased beta-cell mass [1].
  • In clear contrast to the NEU3 case, the levels of mRNA for this sialidase were found by quantitative RT-PCR to be markedly decreased in colon cancers [2].
  • Here we demonstrate that NEU3 mRNA level are increased in renal cell carcinomas (RCCs) compared with adjacent non-tumor tissues, significantly correlating with elevation of interleukin-6 (IL-6), a pleiotropic cytokine that has been implicated in immune responses and pathogenesis of several cancers, including RCCs [3].
  • Lysosomal and plasma membrane sialidase activities in lymphocytes were studied in four patients with sialidosis with partial beta-galactosidase deficiency, four obligate heterozygotes, and three siblings of a patient [4].
  • Effects of cell surface ganglioside sialidase inhibition on growth control and differentiation of human neuroblastoma cells [5].

High impact information on NEU3

  • Up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression [6].
  • Human plasma membrane-associated sialidase (Neu3) is unique in specifically hydrolyzing gangliosides, thought to participate in cell differentiation and transmembrane signaling, thereby playing crucial roles in the regulation of cell surface functions [6].
  • Accumulation of GM3 and GM2 gangliosides was found in sympathetic ganglia but a catabolic disturbance of these gangliosides was ruled out by normal levels of GM3 ganglioside sialidase and N-acetyl-beta-hexosaminidase A activities. beta-Galactosidase activity was decreased in leukocytes and fibroblasts, but not in serum [7].
  • In human RCC ACHN cells, IL-6 treatment enhanced NEU3 promoter luciferase activity 2.5-fold and the endogenous sialidase activity significantly [3].
  • Consistent with these data, NEU3 markedly inhibited staurosporine-induced caspase-3 activity and enhanced IL-6-dependent inhibition, which was abolished by LY294002, a PI3K inhibitor [3].

Chemical compound and disease context of NEU3


Biological context of NEU3

  • Transient transfection of NEU3 into 3T3-L1 adipocytes and L6 myocytes caused a significant decrease in IR signaling [1].
  • In response to insulin, NEU3 was found to undergo tyrosine phosphorylation and subsequent association with the Grb2 protein, thus being activated and causing negative regulation of insulin signaling [1].
  • Here we describe the identification and expression of a human plasma-membrane-associated sialidase, NEU3, isolated starting from an expressed sequence tag (EST) clone [10].
  • The polypeptide contains all the typical sialidase amino acid motifs and, apart from an amino acid stretch that appears unique among mammalian sialidases, shows a high degree of homology for NEU2 and the plasma membrane-associated (NEU3) sialidases [11].
  • Particularly, increased expression of NEU3 has been implicated in the survival of various cancer cells and also in the development of insulin resistance [12].

Anatomical context of NEU3


Associations of NEU3 with chemical compounds


Regulatory relationships of NEU3


Other interactions of NEU3


Analytical, diagnostic and therapeutic context of NEU3


  1. Overexpression of plasma membrane-associated sialidase attenuates insulin signaling in transgenic mice. Sasaki, A., Hata, K., Suzuki, S., Sawada, M., Wada, T., Yamaguchi, K., Obinata, M., Tateno, H., Suzuki, H., Miyagi, T. J. Biol. Chem. (2003) [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. Plasma membrane-associated sialidase is up-regulated in renal cell carcinoma and promotes interleukin-6-induced apoptosis suppression and cell motility. Ueno, S., Saito, S., Wada, T., Yamaguchi, K., Satoh, M., Arai, Y., Miyagi, T. J. Biol. Chem. (2006) [Pubmed]
  4. Carrier detection of sialidosis with partial beta-galactosidase deficiency by the assay of lysosomal sialidase in lymphocytes. Tsuji, S., Yamada, T., Ariga, T., Toyoshima, I., Yamaguchi, H., Kitahara, Y., Miyatake, T., Yamakawa, T. Ann. Neurol. (1984) [Pubmed]
  5. Effects of cell surface ganglioside sialidase inhibition on growth control and differentiation of human neuroblastoma cells. Kopitz, J., Mühl, C., Ehemann, V., Lehmann, C., Cantz, M. Eur. J. Cell Biol. (1997) [Pubmed]
  6. Up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression. Kakugawa, Y., Wada, T., Yamaguchi, K., Yamanami, H., Ouchi, K., Sato, I., Miyagi, T. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Adult type neuronal storage disease with neuraminidase deficiency. Miyatake, T., Atsumi, T., Obayashi, T., Mizuno, Y., Ando, S., Ariga, T., Matsui-Nakamura, K., Yamada, T. Ann. Neurol. (1979) [Pubmed]
  8. Negative regulation of neuroblastoma cell growth by carbohydrate-dependent surface binding of galectin-1 and functional divergence from galectin-3. Kopitz, J., von Reitzenstein, C., André, S., Kaltner, H., Uhl, J., Ehemann, V., Cantz, M., Gabius, H.J. J. Biol. Chem. (2001) [Pubmed]
  9. Galectin-1 is a major receptor for ganglioside GM1, a product of the growth-controlling activity of a cell surface ganglioside sialidase, on human neuroblastoma cells in culture. Kopitz, J., von Reitzenstein, C., Burchert, M., Cantz, M., Gabius, H.J. J. Biol. Chem. (1998) [Pubmed]
  10. Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane. Monti, E., Bassi, M.T., Papini, N., Riboni, M., Manzoni, M., Venerando, B., Croci, G., Preti, A., Ballabio, A., Tettamanti, G., Borsani, G. Biochem. J. (2000) [Pubmed]
  11. 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]
  12. Homology modeling of human sialidase enzymes NEU1, NEU3 and NEU4 based on the crystal structure of NEU2: Hints for the design of selective NEU3 inhibitors. Magesh, S., Suzuki, T., Miyagi, T., Ishida, H., Kiso, M. J. Mol. Graph. Model. (2006) [Pubmed]
  13. Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages. Stamatos, N.M., Liang, F., Nan, X., Landry, K., Cross, A.S., Wang, L.X., Pshezhetsky, A.V. FEBS J. (2005) [Pubmed]
  14. Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles. Yamaguchi, K., Hata, K., Wada, T., Moriya, S., Miyagi, T. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. A close association of the ganglioside-specific sialidase Neu3 with caveolin in membrane microdomains. Wang, Y., Yamaguchi, K., Wada, T., Hata, K., Zhao, X., Fujimoto, T., Miyagi, T. J. Biol. Chem. (2002) [Pubmed]
  16. Plasma-membrane-associated sialidase (NEU3) differentially regulates integrin-mediated cell proliferation through laminin- and fibronectin-derived signalling. Kato, K., Shiga, K., Yamaguchi, K., Hata, K., Kobayashi, T., Miyazaki, K., Saijo, S., Miyagi, T. Biochem. J. (2006) [Pubmed]
  17. Dependence of neurotrophic factor activation of Trk tyrosine kinase receptors on cellular sialidase. Woronowicz, A., Amith, S.R., De Vusser, K., Laroy, W., Contreras, R., Basta, S., Szewczuk, M.R. Glycobiology (2007) [Pubmed]
  18. Role of plasma membrane ganglioside sialidase of human neuroblastoma cells in growth control and differentiation. Kopitz, J., von Reitzenstein, C., Mühl, C., Cantz, M. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  19. The plasma membrane ganglioside sialidase cofractionates with markers of lipid rafts. Kalka, D., von Reitzenstein, C., Kopitz, J., Cantz, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  20. Site-directed mutagenesis of human membrane-associated ganglioside sialidase: identification of amino-acid residues contributing to substrate specificity. Wang, Y., Yamaguchi, K., Shimada, Y., Zhao, X., Miyagi, T. Eur. J. Biochem. (2001) [Pubmed]
WikiGenes - Universities