Carbohydrate (Chondroitin 6) Sulfotransferase 3; Carbohydrate (N-Acetylglucosamine 6-O) Sulfotransferase 7 (CHST3,7)

  • Osami Habuchi
Reference work entry


Chondroitin sulfate chains are composed of GlcAβ1-3GalNAcβ1-4 repeating unit with sulfate groups on GalNAc residues or on both GalNAc and GlcA residues. Sulfate groups attached to the backbone sugar chain produce various chondroitin sulfate isomers. Chondroitin 6-sulfate, which contains sulfate at position 6 of the GalNAc residue, is one of the major components of aggrecan and is thought to be involved in the formation and maintenance of cartilage. Chondroitin 6-sulfate is also contained in other various proteoglycans, such as phosphacan/PTPz, and is proposed to be involved in neuronal cell interactions with growth factors pleiotrophin and midkine (Maeda et al. 1996, 1999). Chondroitin 6-sulfotransferase (C6ST) catalyzes the transfer of sulfate to position 6 of GalNAc residues of chondroitin. Two C6STs, C6ST-1 (CHST-3) and C6ST-2 (CHST-7), were cloned. C6ST-1 also sulfates 6-position of the Gal residue of keratan sulfate and sialyl N-acetyllactosamine oligosaccharides.


Chondroitin Sulfate Keratan Sulfate Sciatic Nerve Crush GlcNAc Residue Chondroitin Sulfate Chain 
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  1. Akama TO, Nishida K, Nakayama J, Watanabe H, Ozaki K, Nakamura T, Dota A, Kawasaki S, Inoue Y, Maeda N, Yamamoto S, Fujiwara T, Thonar EJ, Shimomura Y, Kinoshita S, Tanigami A, Fukuda MN (2000) Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene. Nat Genet 26:237–241PubMedCrossRefGoogle Scholar
  2. Bhakta S, Bartes A, Bowman KG, Kao WM, Polsky I, Lee JK, Cook BN, Bruehl RE, Rosen SD, Bertozzi CR, Hemmerich S (2000) Sulfation of N-acetylglucosamine by chondroitin 6-sulfotransferase 2 (GST-5). J Biol Chem 275:40226–40234PubMedCrossRefGoogle Scholar
  3. Bistrup A, Bhakta S, Lee JK, Belov YY, Gunn MD, Zuo F-R, Huang C-C, Kannagi R, Rosen SD, Hemmerich S (1999) Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligand for L-selectin. J Cell Biol 145:899–910PubMedCrossRefGoogle Scholar
  4. Bowe MA, Deyst KA, Leszyk JD, Fallon J (1994) Identification and purification of an agrin receptor from Torpedo postsynaptic membranes: a heteromeric complex related to the dystroglycans. Neuron 12:1173–1180PubMedCrossRefGoogle Scholar
  5. 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
  6. 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
  7. 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
  8. Habuchi O, Miyata K (1980) Stimulation of glycosaminoglycan sulfotransferase from chick embryo cartilage by basic proteins and polyamines. Biochim Biophys Acta 616:208–217PubMedCrossRefGoogle Scholar
  9. Habuchi O, Miyashita N (1982) Separation and characterization of chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase from chick embryo cartilage. Biochim Biophys Acta 717:414–421PubMedCrossRefGoogle Scholar
  10. Habuchi O, Tsuzuki M, Takeuchi I, Hara M, Matsui Y, Ashikari S (1991) Secretion of chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase from cultured chick embryo chondrocytes. Biochim Biophys Acta 1133:9–16PubMedCrossRefGoogle Scholar
  11. Habuchi O, Matsui Y, Kotoya Y, Aoyama Y, Yasuda Y, Noda M (1993) Purification of chondroitin 6-sulfotransferase secreted from cultured chick embryo chondrocytes. J Biol Chem 268:21968–21974PubMedGoogle Scholar
  12. 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
  13. Habuchi O, Suzuki Y, Fukuta M (1997) Sulfation of sialyl lactosamine oligosaccharides by chondroitin 6-sulfotransferase. Glycobiology 7:405–412PubMedCrossRefGoogle Scholar
  14. Hermanns P, Unger S, Rossi A, Perez-Aytes A, Cortina H, Bonafé L, Boccone L, Setzu V, Dutoit M, Sangiorgi L, Pecora F, Reicherter K, Nishimura G, Spranger J, Zabel B, Superti-Furga A (2008) Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis. Am J Hum Genet 82:1368–1374PubMedCentralPubMedCrossRefGoogle Scholar
  15. Hiraoka N, Petryniak B, Nakayama J, Tsuboi S, Suzuki M, Yeh JC, 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
  16. Inoue H, Otsu K, Yoneda M, Kimata K, Suzuki S, Nakanishi Y (1986) Glycosaminoglycan sulfotransferases in human and animal sera. J Biol Chem 261:4460–4469PubMedGoogle Scholar
  17. Kitagawa H, Fujita M, Ito N, Sugahara K (2000) Molecular cloning and expression of a novel chondroitin 6-O-sulfotransferase. J Biol Chem 275:21075–21080PubMedCrossRefGoogle Scholar
  18. Kitagawa H, Tsutsumi K, Ikegami-Kuzuhara A, Nadanaka S, Goto F, Ogawa T, Sugahara K (2008) Sulfation of the galactose residues in the glycosaminoglycan-protein linkage region by recombinant human chondroitin 6-O-sulfotransferase-1. J Biol Chem 283:27438–27443PubMedCrossRefGoogle Scholar
  19. Kitagawa H, Tsutsumi K, Tone Y, Sugahara K (1997) Developmental regulation of the sulfation profile of chondroitin sulfate chains in the chicken embryo brain. J Biol Chem 272:31377–31381PubMedCrossRefGoogle Scholar
  20. Lee JK, Bhakta S, Rosen SD, Hemmerich S (1999) Cloning and characterization of mammalian N-acetylglucosamine-6-sulfotransferase that is highly restricted to intestinal tissue. Biochem Biophys Res Commun 263:543–549PubMedCrossRefGoogle Scholar
  21. Lin R, Rosahl TW, Whiting PJ, Fawcett JW, Kwok JC (2011) 6-Sulphated chondroitins have a positive influence on axonal regeneration. PLoS One 6:e21499PubMedCentralPubMedCrossRefGoogle Scholar
  22. Liu J, Chau CH, Liu H, Jang BR, Li X, Chan YS, Shum DK (2006) Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth. J Cell Sci 119:933–942PubMedCrossRefGoogle Scholar
  23. Maeda N, Nishiwaki T, Shintani T, Hamanaka H, Noda M (1996) 6B4 proteoglycan/phosphacan, an extracellular variant of receptor-like protein-tyrosine phosphatase zeta/RPTPbeta, binds pleiotrophin/heparin-binding growth-associated molecule (HB-GAM). J Biol Chem 271:21446–21452PubMedCrossRefGoogle Scholar
  24. Maeda N, Ichihara-Tanaka K, Kimura T, Kadomatsu K, Muramatsu T, Noda M (1999) A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a heparin-binding growth factor midkine. Involvement of arginine 78 of midkine in the high affinity binding to PTPzeta. J Biol Chem 274:12474–12479PubMedCrossRefGoogle Scholar
  25. Miyata S, Komatsu Y, Yoshimura Y, Taya C, Kitagawa H (2012) Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nat Neurosci 15:414–422PubMedCrossRefGoogle Scholar
  26. Monberg M, Stuhlsatz HW, Kisters R, Greiling H (1972) Isolierung und Substratspezifität einer 3′-Phpsphoadenylylsulfat: Chondroitin-6-Sulfotransferase aus der Mäuseleber. Hoppe Seyler’s Z Physiol Chem 353:1351–1361CrossRefGoogle Scholar
  27. Nastuk MA, Davis A, Yancopoulos GD, Fallon JR (1998) Expression cloning and characterization of NSIST, a novel sulfotransferase expressed by a subset of neurons and postsynaptic targets. J Neurosci 18:7167–7177PubMedGoogle Scholar
  28. Properzi F, Carulli D, Asher RA, Muir E, Camargo LM, van Kuppevelt TH, ten Dam GB, Furukawa Y, Mikami T, Sugahara K, Toida T, Geller HM, Fawcett JW (2005) Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia. Eur J Neurosci 21:378–390PubMedCrossRefGoogle Scholar
  29. Sugumaran G, Katsman M, Drake RR (1995) Purification, photoaffinity labeling, and characterization of a single enzyme for 6-sulfation of both chondroitin sulfate and keratan sulfate. J Biol Chem 270:22483–22484PubMedCrossRefGoogle Scholar
  30. Suzuki S, Strominger JL (1960) Enzymatic sulfation of mucopolysaccharides in hen oviduct. I. Transfer of sulfate from 3′-phosphoadenosine 5′-phosphosulfate to mucopolysaccharides. J Biol Chem 235:257–266PubMedGoogle Scholar
  31. Thiele H, Sakano M, Kitagawa H, Sugahara K, Rajab A, Hohne W, Ritter H, Leschik G, Nurnberg P, Mundlos S (2004) Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement. Proc Nat Acad Sci 101:10155–10160PubMedCrossRefGoogle Scholar
  32. Tsutsumi K, Shimakawa H, Kitagawa H, Sugahara K (1998) Functional expression and genomic structure of human chondroitin 6-sulfotransferase. FEBS Lett 441:235–241PubMedCrossRefGoogle Scholar
  33. Tuysuz B, Mizumoto S, Sugahara K, Celebi A, Mundlos S, Turkmen S (2009) Omani-type spondyloepiphyseal dysplasia with cardiac involvement caused by a missense mutation in CHST3. Clin Genet 75:375–383PubMedCrossRefGoogle Scholar
  34. Uchimura K, Kadomatsu K, Fan Q-W, 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
  35. Uchimura K, Muramatsu H, Kadomatsu K, Fan Q-W, 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
  36. Uchimura K, Fasakhany F, Kadomatsu K, Matsukawa T, Yamakawa T, Kurosawa N, Muramatsu T (2000) Diversity of N-acetylglucosamine-6-O-sulfotransferases: molecular cloning of a novel enzyme with different distribution and specificities. Biochem Biophys Res Commun 274:291–296PubMedCrossRefGoogle Scholar
  37. Uchimura K, Kadomatsu K, Nishimura H, Muramatsu H, Nakamura E, Kurosawa N, Habuchi O, El-Fasakhany FM, Yoshikai Y, Muramatsu T (2002) Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development, and oversulfated chondroitin sulfates. J Biol Chem 277:1443–1450PubMedCrossRefGoogle Scholar
  38. Unger S, Lausch E, Rossi A, Mégarbané A, Sillence D, Alcausin M, Aytes A, Mendoza-Londono R, Nampoothiri S, Afroze B, Hall B, Lo IF, Lam ST, Hoefele J, Rost I, Wakeling E, Mangold E, Godbole K, Vatanavicharn N, Franco LM, Chandler K, Hollander S, Velten T, Reicherter K, Spranger J, Robertson S, Bonafé L, Zabel B, Superti-Furga A (2010) Phenotypic features of carbohydrate sulfotransferase 3 (CHST3) deficiency in 24 patients: congenital dislocations and vertebral changes as principal diagnostic features. Am J Med Genet A 152A:2543–2549PubMedCrossRefGoogle Scholar
  39. van Roij MHH, Mizumoto S, Yamada S, Morgan T, Tan-Sindhunata MB, Meijers-Heijboer H, Verbeke JILM, Markie D, Sugahara K, Robertson SP (2008) Spondyloepiphyseal dysplasia, Omani type: further definition of the phenotype. Am J Med Genet 146A:2376–2384PubMedCrossRefGoogle Scholar
  40. Yamada T, Ohtake S, Sato M, Habuchi O (2004) Chondroitin 4-sulphotransferase-1 and chondroitin 6-sulphotransferase-1 are affected differently by uronic acid residues neighbouring the acceptor GalNAc residues. Biochem J 384:567–575PubMedCrossRefGoogle Scholar
  41. Yusa A, Kitajima K, Habuchi O (2006) N-linked oligosaccharides on chondroitin 6-sulfotransferase-1 are required for production of the active enzyme, Golgi localization, and sulfotransferase activity toward keratan sulfate. J Biol Chem 281:20393–20403PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Advanced Medical Research CenterAichi Medical UniversityNagakuteJapan

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