Gene Symbol: NEU4
Description: neuraminidase 4
Alias: sialidase-4, N-acetyl-alpha-neuraminidase 4, neuraminidase 4 (sialidase)
Species: human
Products:     NEU4

Top Publications

  1. Cai B, Wu P, Chou C, Huang H, Chao C, Chung H, et al. Synergistic activation of the NEU4 promoter by p73 and AP2 in colon cancer cells. Sci Rep. 2019;9:950 pubmed publisher
    ..The AP2 family also acts as a tumor suppressor. Here we found that p73 and AP2 are able to activate NEU4, a neuraminidase gene, which removes the terminal sialic acid residues from cancer-associated glycans...
  2. Demina E, Pierre W, Nguyen A, Londono I, Reiz B, Zou C, et al. Persistent reduction in sialylation of cerebral glycoproteins following postnatal inflammatory exposure. J Neuroinflammation. 2018;15:336 pubmed publisher
    ..Together, our data demonstrate that neonatal LPS exposure results in specific and sustained induction of Neu1 and Neu4, causing long-lasting negative changes in sialylation of glycoproteins on brain cells...
  3. Glanz V, Myasoedova V, Grechko A, Orekhov A. Sialidase activity in human pathologies. Eur J Pharmacol. 2019;842:345-350 pubmed publisher
    ..Four types of mammalian sialidases have been described: NEU1, NEU2, NEU3 and NEU4. They are encoded by different genes and characterized by different subcellular localization...
  4. Finlay T, Jayanth P, Amith S, Gilmour A, Guzzo C, Gee K, et al. Thymoquinone from nutraceutical black cumin oil activates Neu4 sialidase in live macrophage, dendritic, and normal and type I sialidosis human fibroblast cells via GPCR Galphai proteins and matrix metalloproteinase-9. Glycoconj J. 2010;27:329-48 pubmed publisher
    ..have no inhibition of TQ-induced sialidase activity in live BMC-2 and human THP-1 macrophage cells but anti-Neu4 antibodies completely block this activity...
  5. Finlay T, Abdulkhalek S, Gilmour A, Guzzo C, Jayanth P, Amith S, et al. Thymoquinone-induced Neu4 sialidase activates NF?B in macrophage cells and pro-inflammatory cytokines in vivo. Glycoconj J. 2010;27:583-600 pubmed publisher
    Thymoquinone (TQ) derived from the nutraceutical black cumin oil has been reported to be a novel agonist of Neu4 sialidase activity in live cells (Glycoconj J DOI 10.1007/s10719-010-9281-6)...
  6. Pshezhetsky A, Ashmarina M. Keeping it trim: roles of neuraminidases in CNS function. Glycoconj J. 2018;35:375-386 pubmed publisher
    ..Emerging data demonstrate that these enzymes with different, yet overlapping expression patterns, intracellular localization and substrate specificity play essential roles in the physiology of the CNS. ..
  7. Richards M, Guo T, Hunter C, Cairo C. Molecular dynamics simulations of viral neuraminidase inhibitors with the human neuraminidase enzymes: Insights into isoenzyme selectivity. Bioorg Med Chem. 2018;26:5349-5358 pubmed publisher
    ..Humans can express multiple forms of neuraminidase enzymes (NEU1, NEU2, NEU3, NEU4) that share a similar active site and enzymatic mechanism with their viral counterparts...
  8. Kim S, Becker J, Bechheim M, Kaiser V, Noursadeghi M, Fricker N, et al. Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes. Nat Commun. 2014;5:5236 pubmed publisher
    ..Among these we find functional SNPs for the expression of NEU4, CCL14, CBX3 and IRF5 on TLR4 activation...
  9. Chigwechokha P, Komatsu M, Itakura T, Shiozaki K. Nile Tilapia Neu3 sialidases: molecular cloning, functional characterization and expression in Oreochromis niloticus. Gene. 2014;552:155-64 pubmed publisher
    ..A tilapia genome-wide search for orthologues of human NEU1, NEU2, NEU3 and NEU4 yielded eight putative tilapia sialidases, five of which were neu3-like and designated as neu3a, neu3b, neu3c, ..

More Information


  1. Urashima T, Inamori H, Fukuda K, Saito T, Messer M, Oftedal O. 4-O-Acetyl-sialic acid (Neu4,5Ac2) in acidic milk oligosaccharides of the platypus (Ornithorhynchus anatinus) and its evolutionary significance. Glycobiology. 2015;25:683-97 pubmed publisher
    ..The primary saccharide in long-beaked echidna milk is an acidic trisaccharide Neu4,5Ac2(α2-3)Gal(β1-4)Glc (4-O-acetyl 3'-sialyllactose), but acidic oligosaccharides have not been characterized ..
  2. Di Rosa M, Sanfilippo C, Libra M, Musumeci G, Malaguarnera L. Different pediatric brain tumors are associated with different gene expression profiling. Acta Histochem. 2015;117:477-85 pubmed publisher
    ..In addition evaluating other lisosomal enzymes such as glycosidases and proteases we found that NEU4, CTBS and GBA2 belonging to glycosidases family and CTSC, CTSK and CTSF belonging to proteases family were ..
  3. Honda A, Chigwechokha P, Kamada Futagami Y, Komatsu M, Shiozaki K. Unique nuclear localization of Nile tilapia (Oreochromis niloticus) Neu4 sialidase is regulated by nuclear transport receptor importin ?/?. Biochimie. 2018;149:92-104 pubmed publisher
    Sialidase catalyzes the removal of sialic acids from glycoconjugates. Different from Neu1 and Neu3 sialidases, Neu4 enzymatic properties such as substrate specificity and subcellular localization are not well-conserved among vertebrates...
  4. Miyagi T, Takahashi K, Yamamoto K, Shiozaki K, Yamaguchi K. Biological and Pathological Roles of Ganglioside Sialidases. Prog Mol Biol Transl Sci. 2018;156:121-150 pubmed publisher
    ..In mammals, there are four forms of sialidase (Neu1, Neu2, Neu3, and Neu4), differing in their major subcellular localization and enzymatic properties...
  5. Katorcha E, Klimova N, Makarava N, Savtchenko R, Pan X, Annunziata I, et al. Loss of Cellular Sialidases Does Not Affect the Sialylation Status of the Prion Protein but Increases the Amounts of Its Proteolytic Fragment C1. PLoS ONE. 2015;10:e0143218 pubmed publisher
    ..Of the four known mammalian sialidases, the enzymes that cleave off sialic acid residues, only NEU1, NEU3 and NEU4 are expressed in the brain...
  6. Ryuzono S, Takase R, Oishi K, Ikeda A, Chigwechokha P, Funahashi A, et al. Lysosomal localization of Japanese medaka (Oryzias latipes) Neu1 sialidase and its highly conserved enzymatic profiles with human. Gene. 2016;575:513-523 pubmed publisher
    ..tissues, and its expression level was significantly higher than other sialidase genes such as neu3a, neu3b and neu4. The present study revealed the profiles of fish Neu1 sialidase and indicated its high conservation with human NEU1 ..
  7. Yu H, Zeng J, Li Y, Thon V, Shi B, Chen X. Effective one-pot multienzyme (OPME) synthesis of monotreme milk oligosaccharides and other sialosides containing 4-O-acetyl sialic acid. Org Biomol Chem. 2016;14:8586-97 pubmed publisher
    A facile one-pot two-enzyme chemoenzymatic approach has been established for the gram (Neu4,5Ac2?3Lac, 1.33 g) and preparative scale (Neu4,5Ac2?3LNnT) synthesis of monotreme milk oligosaccharides...
  8. Minami A, Saito M, Mamada S, Ieno D, Hikita T, Takahashi T, et al. Role of Sialidase in Long-Term Potentiation at Mossy Fiber-CA3 Synapses and Hippocampus-Dependent Spatial Memory. PLoS ONE. 2016;11:e0165257 pubmed publisher
    ..Sialidase (EC, which has 4 isozymes including Neu1, Neu2, Neu3 and Neu4, regulates the sialylation level of glycans by removing sialic acid from sialylglycoconjugate...
  9. Monti E, Bassi M, Bresciani R, Civini S, Croci G, Papini N, et al. Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family. Genomics. 2004;83:445-53 pubmed
    ..The NEU4 gene, identified by searching sequence databases for entries showing homologies to the human cytosolic sialidase ..
  10. Bigi A, Tringali C, Forcella M, Mozzi A, Venerando B, Monti E, et al. A proline-rich loop mediates specific functions of human sialidase NEU4 in SK-N-BE neuronal differentiation. Glycobiology. 2013;23:1499-509 pubmed publisher
    Human sialidase NEU4 long (N4L) is a membrane-associated enzyme that has been shown to be localized in the outer mitochondrial membrane...
  11. Silvestri I, Testa F, Zappasodi R, Cairo C, Zhang Y, Lupo B, et al. Sialidase NEU4 is involved in glioblastoma stem cell survival. Cell Death Dis. 2014;5:e1381 pubmed publisher
    The human sialidase, NEU4, has emerged as a possible regulator of neuronal differentiation and its overexpression has been demonstrated to promote the acquisition of a stem cell-like phenotype in neuroblastoma cells...
  12. Shiozaki K, Yamaguchi K, Takahashi K, Moriya S, Miyagi T. Regulation of sialyl Lewis antigen expression in colon cancer cells by sialidase NEU4. J Biol Chem. 2011;286:21052-61 pubmed publisher
    ..However, regulation mechanisms are not fully understood. We previously demonstrated that NEU4 is the only sialidase efficiently acting on mucins and it is down-regulated in colon cancer...
  13. Comelli E, Amado M, Lustig S, Paulson J. Identification and expression of Neu4, a novel murine sialidase. Gene. 2003;321:155-61 pubmed
    ..reported in the Celera database is shown to encode a novel neuraminidase, designated as murine neuraminidase 4 (Neu4). The complete gene contains four exons and an open reading frame of 501 amino acids...
  14. Jia F, Howlader M, Cairo C. Integrin-mediated cell migration is blocked by inhibitors of human neuraminidase. Biochim Biophys Acta. 2016;1861:1170-1179 pubmed publisher
    ..Using a scratch assay, we found that exogenously added Neu3 and Neu4 activity altered rates of cell migration...
  15. Seyrantepe V, Landry K, Trudel S, Hassan J, Morales C, Pshezhetsky A. Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells. J Biol Chem. 2004;279:37021-9 pubmed
    ..In this study we describe a novel lysosomal lumen sialidase encoded by the NEU4 gene on human chromosome 2...
  16. Stamatos N, Liang F, Nan X, Landry K, Cross A, Wang L, et al. Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages. FEBS J. 2005;272:2545-56 pubmed
    ..In this study, we demonstrate that three of these sialidases, lysosomal Neu1 and Neu4 and plasma membrane-associated Neu3, are expressed in human monocytes...
  17. Miyagi T, Wada T, Yamaguchi K, Shiozaki K, Sato I, Kakugawa Y, et al. Human sialidase as a cancer marker. Proteomics. 2008;8:3303-11 pubmed publisher
    ..Human sialidases are indeed related to malignancy and may be potential targets for cancer diagnosis and therapy. ..
  18. Bigi A, Morosi L, Pozzi C, Forcella M, Tettamanti G, Venerando B, et al. Human sialidase NEU4 long and short are extrinsic proteins bound to outer mitochondrial membrane and the endoplasmic reticulum, respectively. Glycobiology. 2010;20:148-57 pubmed publisher
    ..b>NEU4, the most recently identified member of the human sialidase family, is found in two forms, NEU4 long and NEU4 short,..
  19. Tringali C, Cirillo F, Lamorte G, Papini N, Anastasia L, Lupo B, et al. NEU4L sialidase overexpression promotes ?-catenin signaling in neuroblastoma cells, enhancing stem-like malignant cell growth. Int J Cancer. 2012;131:1768-78 pubmed publisher
    ..In this article, we demonstrate that sialidase NEU4 long (NEU4L) influences the differentiation/proliferation behavior of NB SK-N-BE cells by determining ..
  20. Takahashi K, Mitoma J, Hosono M, Shiozaki K, Sato C, Yamaguchi K, et al. Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and negatively regulates neurite formation by hippocampal neurons. J Biol Chem. 2012;287:14816-26 pubmed publisher
    ..In the present study, we identified and characterized a murine sialidase NEU4 that catalytically degrades polySia...