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Chemical Compound Review

Man-6-p     [(2R,3S,4S,5S)-3,4,5,6- tetrahydroxyoxan-2...

Synonyms: SureCN345396, CHEBI:48066, AC1Q6RVE, AC1L22NJ, C00275, ...
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Disease relevance of Mannose 6-phosphate

  • Mucolipidosis II (ML II) is a fatal lysosomal storage disorder resulting from defects in the multimeric GlcNAc-1-phosphotransferase responsible for the initial step in the generation of the mannose 6-phosphate (M6P) recognition marker [1].
  • We conclude that in breast cancer cells, even though procath-D interacts intracellularly and extracellarly with prosaposin, it is endocytosed independent of prosaposin by a receptor different from the M6P receptors and the LRP [2].
  • We compared two recombinant alpha-galactosidases developed for enzyme replacement therapy for Fabry disease, agalsidase alfa and agalsidase beta, as to specific alpha-galactosidase activity, stability in plasma, mannose 6-phosphate (M6P) residue content, and effects on cultured human Fabry fibroblasts and Fabry mice [3].

High impact information on Mannose 6-phosphate

  • M6P residues on oligosaccharides of newly synthesized lysosomal enzymes are essential for efficient receptor-mediated transport to lysosomes [1].
  • We have previously reported that lymphocyte attachment to PN HEV is selectively inhibited by mannose-6-phosphate (M6P) and related carbohydrates (Stoolman, L. M., T. S. Tenforde, and S. D. Rosen, 1984, J. Cell Biol., 99:1535-1540) [4].
  • The Tat motif allowed for mannose-6-phosphate (M6P) independent uptake in vitro and significantly increased the distribution of beta-glucuronidase secreted from transduced cells after intravenous or direct brain injection in mice of recombinant vectors [5].
  • Collectively, these data suggest that different carbohydrate structures are involved in the entry of lymphocytes into different lymphoid organs, with mannose recognition playing an important role in splenic entry and recognition of M6P-like structures controlling lymph node entry [6].
  • In this study, we evaluate the potential of liver-directed gene therapy, that is, programming of murine hepatocytes to secrete the enzyme with mannose 6-phosphate (M6P), which can be taken up by distant cells [7].

Biological context of Mannose 6-phosphate


Anatomical context of Mannose 6-phosphate


Associations of Mannose 6-phosphate with other chemical compounds

  • In contrast, it was found that mannose-and M6P-containing structures, unlike sulfated polysaccharides such as fucoidan, did not affect the subsequent positioning of lymphocytes within lymphoid organs [6].
  • In contrast, mannose 6 phosphate (M6P) did not alter RA or IGF-II actions [10].

Gene context of Mannose 6-phosphate

  • In fibroblasts, we confirmed that the endocytosis of these two proteins was different since it was generally mediated by the M6P receptors for procath-D and mostly by LRP (LDL receptor-related protein) for prosaposin [2].
  • The effectiveness of these two phosphomonosaccharides varied depending on the source of the enzyme: ileal beta-NAG-ligatin complexes showed a four-fold preferential dissociation with Man6P; macrophage complexes showed a 160-fold preferential dissociation with Glc 1P [11].
  • Gene therapy could program liver to secrete enzyme with mannose 6-phosphate (M6P), and enzyme in blood could be taken up by other cells via the M6P receptor [12].
  • Mono- and bivalent ligands bearing mannose 6-phosphate (M6P) surrogates: targeting the M6P/insulin-like growth factor II receptor [13].
  • Our data indicate that the transfected as well as the infected cells produce a large amount of the IDS enzyme, which is efficiently endocytosed into neuronal and glial cells through the mannose 6-phosphate (M6P) receptor system [14].

Analytical, diagnostic and therapeutic context of Mannose 6-phosphate

  • The solubilized beta-NAG bound to ligatin in vitro as demonstrated by affinity chromatography using the immobilized receptor. beta-N-Acetyl D-glucosaminidase-ligatin complexes were dissociated by low concentrations of mannose 6-phosphate (Man6P) and/or glucose 1-phosphate (Glc 1P) [11].


  1. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Tiede, S., Storch, S., Lübke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. Nat. Med. (2005) [Pubmed]
  2. Procathepsin D interacts with prosaposin in cancer cells but its internalization is not mediated by LDL receptor-related protein. Laurent-Matha, V., Lucas, A., Huttler, S., Sandhoff, K., Garcia, M., Rochefort, H. Exp. Cell Res. (2002) [Pubmed]
  3. Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice. Sakuraba, H., Murata-Ohsawa, M., Kawashima, I., Tajima, Y., Kotani, M., Ohshima, T., Chiba, Y., Takashiba, M., Jigami, Y., Fukushige, T., Kanzaki, T., Itoh, K. J. Hum. Genet. (2006) [Pubmed]
  4. Phosphomannosyl-derivatized beads detect a receptor involved in lymphocyte homing. Yednock, T.A., Stoolman, L.M., Rosen, S.D. J. Cell Biol. (1987) [Pubmed]
  5. The HIV Tat protein transduction domain improves the biodistribution of beta-glucuronidase expressed from recombinant viral vectors. Xia, H., Mao, Q., Davidson, B.L. Nat. Biotechnol. (2001) [Pubmed]
  6. Modification of lymphocyte migration by mannans and phosphomannans. Different carbohydrate structures control entry of lymphocytes into spleen and lymph nodes. Weston, S.A., Parish, C.R. J. Immunol. (1991) [Pubmed]
  7. Limited transgene immune response and long-term expression of human alpha-L-iduronidase in young adult mice with mucopolysaccharidosis type I by liver-directed gene therapy. Di Domenico, C., Di Napoli, D., Gonzalez Y Reyero, E., Lombardo, A., Naldini, L., Di Natale, P. Hum. Gene Ther. (2006) [Pubmed]
  8. Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophages. Muschol, N., Matzner, U., Tiede, S., Gieselmann, V., Ullrich, K., Braulke, T. Biochem. J. (2002) [Pubmed]
  9. Evidence that lymphocyte traffic into rejecting cardiac allografts is CD11a- and CD49d-dependent. Turunen, J.P., Mattila, P., Halttunen, J., Häyry, P., Renkonen, R. Transplantation (1992) [Pubmed]
  10. Role of the IGF-II receptor in mediating acute, non-genomic effects of retinoids and IGF-II on keratinocyte cell death. Louafi, F., Stewart, C.E., Perks, C.M., Thomas, M.G., Holly, J.M. Exp. Dermatol. (2003) [Pubmed]
  11. Ligatin binds phosphohexose residues on acidic hydrolases. Jakoi, E.R., Kempe, K., Gaston, S.M. Journal of supramolecular structure and cellular biochemistry. (1981) [Pubmed]
  12. Liver-directed neonatal gene therapy prevents cardiac, bone, ear, and eye disease in mucopolysaccharidosis I mice. Liu, Y., Xu, L., Hennig, A.K., Kovacs, A., Fu, A., Chung, S., Lee, D., Wang, B., Herati, R.S., Mosinger Ogilvie, J., Cai, S.R., Parker Ponder, K. Mol. Ther. (2005) [Pubmed]
  13. Mono- and bivalent ligands bearing mannose 6-phosphate (M6P) surrogates: targeting the M6P/insulin-like growth factor II receptor. Berkowitz, D.B., Maiti, G., Charette, B.D., Dreis, C.D., MacDonald, R.G. Org. Lett. (2004) [Pubmed]
  14. Uptake of recombinant iduronate-2-sulfatase into neuronal and glial cells in vitro. Daniele, A., Tomanin, R., Villani, G.R., Zacchello, F., Scarpa, M., Di Natale, P. Biochim. Biophys. Acta (2002) [Pubmed]
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