Intestinal N-Acetylglucosamine 6-O-Sulfotransferase

  • Stefan Hemmerich


Intestinal N-acetylglucosamine 6-O-sulfotransferase (I-GlcNAc6ST, GST-4, GlcNAc6ST-3) (Lee et al. 1999; Hemmerich and Rosen 2000) is the most recently discovered member of a novel family of carbohydrate sulfotransferases termed galactose, N-acetylgalactosamine, or N-acetylglucosamine 6-O-sulfotransferases (GST) (Rosen et al. 1999; Hemmerich and Rosen 2000). This is a class of five enzymes to date that have a type II membrane organization with a short cytoplasmic tail at the N-termi- nus, a transmembrane domain, and a large luminal C-terminal catalytic domain. I- GlcNAc6ST is one of the three N-acetylglucosamine 6-O-sulfotransferases contained in this family; the other two isozymes are the ubiquitous N-acetylglucosamine 6-O- sulfotransferase (GlcNAc6ST, GST-2, CHST-2) (Li and Tedder 1999; Uchimura et al. 1998b,c) and the high endothelial cell N-acetylglucosamine 6-O-sulfotransferase (HEC-GlcNAc6ST, GST-3) (Bistrup et al. 1999; Hiraoka et al. 1999). The other two enzymes of this family, chondroitin 6-O-sulfotransferase (C6ST, GST-0) (Fukuta et al. 1995, 1998; Uchimura et al. 1998a; Hemmerich and Rosen 1999) and keratan sulfate 6-O-sulfotransferase (KSGal6ST, GST-1, CHST-1) (Fukuta et al. 1997; Li and Tedder 1999; Hemmerich and Rosen 2000), facilitate sulfation at C-6 of galactose within the context of N-acetyllactosamine (Habuchi et al. 1996, 1997; Bistrup et al. 1999), with C6ST also catalyzing sulfation at C-6 of N-acetylgalactosamine within chondroitin (Fukuta et al. 1997). The three GlcNAc6ST isozymes exhibit more than 55% similarity to each other on the amino acid level, and protein sequence similarity across the entire enzyme family is more than 40% (Hemmerich and Rosen 2000). As indicated in the nomenclature, the three N-acetylglucosamine 6-O-sulfotransferases show distinct expression patterns. Thus GlcNAc6ST (GST-2) is abundantly expressed in most tissues and cell types (Uchimura et al. 1998; A. Bistrup, S. Hemmerich, and S.D. Rosen, unpublished), whereas HEC-GlcNAc6ST and I-GlcNAc6ST are remarkably restricted to high endothelial cells or intestinal tissue, respectively (Bistrup et al. 1999; Lee et al. 1999).


Intestinal Tissue Keratan Sulfate Complete Open Reading Frame Acceptor Specificity Lymphocyte Homing 
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  1. Altschul SF, Madden TL, Schäffer AA, Zhang J-H, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402PubMedCrossRefGoogle Scholar
  2. Berg EL, McEvoy LM, Berlin C, Bargatze RF, Butcher EC (1993) L-Selectin-mediated lymphocyte rolling on MAdCAM-1. Nature 366:695–698PubMedCrossRefGoogle Scholar
  3. Bistrup A, Bhakta S, Lee JK, Belov YY, Gunn MD, Zuo FR, Huang CC, Kannagi R, Rosen SD, Hemmerich S (1999) Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin. J Cell Biol 145:899–910PubMedCrossRefGoogle Scholar
  4. Bowman KG, Hemmerich S, Bhakta S, Singer MS, Bistrup A, Rosen SD, Bertozzi CR (1998) Identification of an N-acetylglucosamine-6-O-sulfotransferase activity specific to lymphoid tissue: an enzyme with a possible role in lymphocyte homing. Chem Biol 5:447–460PubMedCrossRefGoogle Scholar
  5. Butcher EC, Picker LJ (1996) Lymphocyte homing and homeostasis. Nature 272:60–66Google Scholar
  6. Degroote S, Lo-Guidice J-M, Strecker G, Ducourouble, M-P, Roussel P, Lamblin G (1997) Characterization of an N-acetylglucosamine-6-O-sulfotransferase from human respiratory mucosa active on mucin carbohydrate chains. J Biol Chem 272:29493–29501PubMedCrossRefGoogle Scholar
  7. Fukuta M, Inazawa J, Torii T, Tsuzuki K, Shimada E, Habuchi O (1997) Molecular cloning and characterization of human keratan sulfate Gal-6-sulfotransferase. J Biol Chem 272:32321–32328PubMedCrossRefGoogle Scholar
  8. Fukuta M, Kobayashi Y, Uchimura K, Kimata K, Habuchi O (1998) Molecular cloning and expression of human chondroitin 6-sulfotransferase. Biochim Biophys Acta 1399:57–61PubMedCrossRefGoogle Scholar
  9. Fukuta M, Uchimura K, Nakashima K, Kato M, Kimata K, Shinomura T, Habuchi O (1995) Molecular cloning and expression of chick chondrocyte chondroitin 6-sulfotransferase. J Biol Chem 270:18575–18580PubMedCrossRefGoogle Scholar
  10. Habuchi O, Hirahara Y, Uchimura K, Fukuta M (1996) Enzymatic sulfation of galactose residue of keratan sulfate by chondroitin 6-sulfotransferase. Glycobiology 6:51–57PubMedCrossRefGoogle Scholar
  11. Habuchi O, Suzuki Y, Fukuta M (1997) Sulfation of sialyl lactosamine oligosaccharides by chondroitin 6-sulfotransferase. Glycobiology 7:405–412PubMedCrossRefGoogle Scholar
  12. Hemmerich S, Rosen SD (1994) 6′-Sulfated, sialyl Lewis X is a major capping group of GlyCAM-1. Biochemistry 33:4830–4835PubMedCrossRefGoogle Scholar
  13. Hemmerich S, Rosen SD (2000) Carbohydrate sulfotransferases in lymphocyte homing. Glycobiology 10:849–856PubMedCrossRefGoogle Scholar
  14. Hemmerich S, Bertozzi CR, Leffler H, Rosen SD (1994a) Identification of the sulfated monosaccharides of GlyCAM-1, an endotheliα1-derived ligand for L-selectin. Biochemistry 33:4820–4829PubMedCrossRefGoogle Scholar
  15. Hemmerich S, Butcher EC, Rosen SD (1994b) Sulfation-dependent recognition of HEV-ligands by L-selectin and MECA 79, an adhesion-blocking mAb. J Exp Med 180:2219–2226PubMedCrossRefGoogle Scholar
  16. Hemmerich S, Leffler H, Rosen SD (1995) Structure of the O-glycans in GlyCAM-1, an endotheliα1-derived ligand for L-selectin. 270:12035–12047Google Scholar
  17. Hiraoka N, Petryniak B, Nakayama J, Tsuboi S, Suzuki M, Yeh J-C, Izawa D, Tanaka T, Miyasaka M, Lowe JB, Fukuda M (1999) A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl lewis x, an L-selectin ligand displayed by CD34. Immunity 11:79–89PubMedCrossRefGoogle Scholar
  18. Imai Y, Lasky LA, Rosen SD (1993) Sulphation requirement for GlyCAM-1, an endothelial ligand for L-selectin. Nature 361:555–557PubMedCrossRefGoogle Scholar
  19. Kakuta Y, Pedersen LG, Pedersen LC, Negishi M (1998) Conserved structural motifs in the sulfotransferase family. Trends Biochem Sci 23:129–130PubMedCrossRefGoogle Scholar
  20. Kimura N, Mitsuoka C, Kanamori A, Hiraiwa N, Uchimura K, Muramatsu T, Tamatani T, Kansas GS, Kannagi R (1999) Reconstitution of functional L-selectin ligands on a cultured human endothelial cell line by cotransfection of cc(1,3) fucosyltransferase VII and newly cloned GlcNAcβ:6-sulfotransferase cDNA. Proc Natl Acad Sci USA 96:4530–4535PubMedCrossRefGoogle Scholar
  21. Lee JK, Bhakta S, Rosen SD, Hemmerich S (1999) Cloning and characterization of a mammalian N-acetylglucosamine-6-sulfotransferase that is highly restricted to intestinal tissue. Biochem Biophys Res Commun 263:543–549PubMedCrossRefGoogle Scholar
  22. Li X, Tedder TF (1999) CHST1 and CHST2 sulfotransferases expressed by human vascular endothelial cells: cDNA cloning, expression, and chromosomal localization. Genomics 55:345–347PubMedCrossRefGoogle Scholar
  23. Rosen SD, Bertozzi CB (1996) Leukocyte adhesion: two selectins converge on sulphate. Curr Biol 6:261–264PubMedCrossRefGoogle Scholar
  24. Rosen SD, Bistrup A, Hemmerich S (2000) Carbohydrate sulfotransferases. In: Ernst B, Sinay P, Hart G (eds) Oligosaccharides in chemistry and biology, vol. 2. Weinheim, Wiley-VCH, pp 245–260Google Scholar
  25. Spiro RG, Yasumoto Y, Bhoyroo V (1996) Characterization of a rat liver Golgi sulphotransferase responsible for the 6-O-sulphation of N-acetylglucosamine residues in beta-linkage to mannose: role in assembly of sialyl-galactosyl-N-acetylglucosamine 6-sulphate sequence of Nl-inked oligosaccharides. Biochem J 319:209–216PubMedGoogle Scholar
  26. Uchimura K, Kadomatsu K, Fan QW, Muramatsu H, Kurosawa N, Kaname T, Yamamura K, Fukuta M, Habuchi O, Muramatsu T (1998a) Mouse chondroitin 6-sulfotransferase: molecular cloning, characterization and chromosomal mapping. Glycobiology 8:489–496PubMedCrossRefGoogle Scholar
  27. Uchimura K, Muramatsu H, Kadomatsu K, Fan QW, Kurosawa N, Mitsuoka C, Kannagi R, Habuchi O, Muramatsu T (1998b) Molecular cloning and characterization of an N-acetylglucosamine-6-O-sulfotransferase. J Biol Chem 273:22577–22583PubMedCrossRefGoogle Scholar
  28. Uchimura K, Muramatsu H, Kaname T, Ogawa H, Yamakawa T, Fan QW, Mitsuoka C, Kannagi R, Habuchi O, Yokoyama I, Yamamura K, Ozaki T, Nakagawara A, Kadomatsu K, Muramatsu T (1998c) Human N-acetylglucosamine-6-O-sulfotransferase involved in the biosynthesis of 6-sulfo sialyl Lewis X: molecular cloning, chromosomal mapping, and expression in various organs and tumor cells. J Biochem (Tokyo) 124:670–678CrossRefGoogle Scholar
  29. Vestweber D, Blanks JE (1999) Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev 79:181–213PubMedGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • Stefan Hemmerich
    • 1
    • 2
  1. 1.Department of Respiratory DiseasesRoche BiosciencePalo AltoUSA
  2. 2.Thios Biotechnology Inc.OaklandUSA

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