Carbohydrate (Chondroitin 4) Sulfotransferase 11-13 (CHST11-13)

  • Osami Habuchi
Reference work entry


Chondroitin 4-sulfate, which contains a sulfate group on position 4 of GalNAc residues, is a major component of cartilage proteoglycans (aggrecan). Chondroitin 4-sulfate is also implicated in the cellular interaction with Plasmodium falciparum-infected erythrocytes (Rogerson et al. 1995; Fried and Duffy 1996). Chondroitin 4-sulfotransferase (C4ST) catalyzes the transfer of sulfate to position 4 of GalNAc residues of chondroitin and is involved in the biosynthesis of chondroitin 4-sulfate. Three isoforms of C4ST, C4ST-1, C4ST-2, and C4ST-3, have been cloned (Yamauchi et al. 2000; Hiraoka et al. 2000; Kang et al. 2002).


Gene Trap GalNAc Residue Costello Syndrome Aggressive Breast Cancer Cell HRAS Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Albertini R, De Luca G, Passi A, Moratti R, Abuja PM (1999) Chondroitin-4-sulfate protects high-density lipoprotein against copper-dependent oxidation. Arch Biochem Biophys 365:143–149PubMedCrossRefGoogle Scholar
  2. Cooney CA, Jousheghany F, Yao-Borengasser A, Phanavanh B, Gomes T, Kieber-Emmons AM, Siegel ER, Suva LJ, Ferrone S, Kieber-Emmons T, Monzavi-Karbassi B (2011) Chondroitin sulfates play a major role in breast cancer metastasis: a role for CSPG4 and CHST11 gene expression in forming surface P-selectin ligands in aggressive breast cancer cells. Breast Cancer Res 13:R58PubMedCentralPubMedCrossRefGoogle Scholar
  3. Duelli A, Rönnberg E, Waern I, Ringvall M, Kolset SO, Pejler G (2009) Mast cell differentiation and activation is closely linked to expression of genes coding for the serglycin proteoglycan core protein and a distinct set of chondroitin sulfate and heparin sulfotransferases. J Immunol 183:7073–7083PubMedCrossRefGoogle Scholar
  4. Fried M, Duffy PE (1996) Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272:1416–1417CrossRefGoogle Scholar
  5. 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
  6. 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
  7. 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
  8. 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
  9. Hiraoka N, Nakagawa H, Ong E, Akama OT, Fukuda MN, Fukuda M (2000) Molecular cloning and expression of two distinct human chondroitin 4-O-sulfotransferases that belong to the HNK-1 sulfotransferase gene family. J Biol Chem 275:20188–20196PubMedCrossRefGoogle Scholar
  10. Izumikawa T, Okuura Y, Koike T, Sakoda N, Kitagawa H (2011) Chondroitin 4-O-sulfotransferase-1 regulates the chain length of chondroitin sulfate in co-operation with chondroitin N-acetylgalactosaminyltransferase-2. Biochem J 434:321–331PubMedCrossRefGoogle Scholar
  11. Izumikawa T, Koike T, Kitagawa H (2012) Chondroitin 4-O-sulfotransferase-2 regulates the number of chondroitin sulfate chains initiated by chondroitin N-acetylgalactosaminyltransferase-1. Biochem J 441:697–705PubMedCrossRefGoogle Scholar
  12. Kang HG, Evers MR, Xia G, Baenziger JU, Schachner M (2002) Molecular cloning and characterization of chondroitin-4-O-sulfotransferase-3. A novel member of the HNK-1 family of sulfotransferases. J Biol Chem 277:34766–34772PubMedCrossRefGoogle Scholar
  13. Karlsson C, Dehne T, Lindahl A, Brittberg M, Pruss A, Sittinger M, Ringe J (2010) Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis. Osteoarthritis Cartilage 18:581–592PubMedCrossRefGoogle Scholar
  14. Kimata K, Okayama M, Oohira A, Suzuki S (1973) Cytodifferentiation and proteoglycan biosynthesis. Mol Cell Biochem 1:211–228PubMedCrossRefGoogle Scholar
  15. Klüppel M (2010) The roles of chondroitin-4-sulfotransferase-1 in development and disease. Prog Mol Biol Transl Sci 93:113–132PubMedCrossRefGoogle Scholar
  16. Klüppel M, Vallis KA, Wrana JL (2002) A high-throughput induction gene trap approach defines C4ST as a target of BMP signaling. Mech Dev 118:77–89PubMedCrossRefGoogle Scholar
  17. Klüppel M, Wight TN, Chan C, Hinek A, Wrana JL (2005) Maintenance of chondroitin sulfation balance by chondroitin-4-sulfotransferase 1 is required for chondrocyte development and growth factor signaling during cartilage morphogenesis. Development 132:3989–4003PubMedCrossRefGoogle Scholar
  18. Klüppel M, Samavarchi-Tehrani P, Liu K, Wrana JL, Hinek A (2012) C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome. Eur J Hum Genet 20:870–877PubMedCrossRefGoogle Scholar
  19. Mikami T, Mizumoto S, Kago N, Kitagawa H, Sugahara K (2003) Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-O-sulfotransferases demonstrated using partially desulfated dermatan sulfate as an acceptor: implication of differential roles in dermatan sulfate biosynthesis. J Biol Chem 278:36115–36127PubMedCrossRefGoogle Scholar
  20. Mizumoto S, Mikami T, Yasunaga D, Kobayashi N, Yamauchi H, Miyake A, Itoh N, Kitagawa H, Sugahara K (2009) Chondroitin 4-O-sulfotransferase-1 is required for somitic muscle development and motor axon guidance in zebrafish. Biochem J 419:387–399PubMedCrossRefGoogle Scholar
  21. Nadanaka S, Ishida M, Ikegami M, Kitagawa H (2008) Chondroitin 4-O-sulfotransferase-1 modulates Wnt-3a signaling through control of E disaccharide expression of chondroitin sulfate. J Biol Chem 283:27333–27343PubMedCrossRefGoogle Scholar
  22. Nadanaka S, Kinouchi H, Taniguchi-Morita K, Tamura J, Kitagawa H (2011) Down-regulation of chondroitin 4-O-sulfotransferase-1 by Wnt signaling triggers diffusion of Wnt-3a. J Biol Chem 286:4199–4208PubMedCrossRefGoogle Scholar
  23. Naujokas MF, Morin M, Anderson MS, Peterson M, Miller J (1993) The chondroitin sulfate form of invariant chain can enhance stimulation of T cell responses through interaction with CD44. Cell 74:257–268PubMedCrossRefGoogle Scholar
  24. Okuda T, Mita S, Yamauchi S, Matsubara T, Yagi F, Yamamori D, Fukuta M, Kuroiwa A, Matsuda Y, Habuchi O (2000) Molecular cloning, expression, and chromosomal mapping of human chondroitin 4-sulfotransferase, whose expression pattern in human tissues is different from that of chondroitin 6-sulfotransferase. J Biochem 128:763–770PubMedCrossRefGoogle Scholar
  25. Robinson HC (1969) The sulphation of chondroitin sulphate in embryonic chicken cartilage. Biochem J 113:543–549PubMedGoogle Scholar
  26. Rogerson SJ, Chaiyaroj SC, Ng K, Reeder JC, Brown GV (1995) Chondroitin sulfate A is a cell surface receptor for Plasmodium falciparum-infected erythrocytes. J Exp Med 182:15–20PubMedCrossRefGoogle Scholar
  27. Schmidt HH, Dyomin VG, Palanisamy N, Itoyama T, Nanjangud G, Pirc-Danoewinata H, Haas OA, Chaganti RS (2004) Deregulation of the carbohydrate (chondroitin 4) sulfotransferase 11 (CHST11) gene in a B-cell chronic lymphocytic leukemia with a t(12;14)(q23;q32). Oncogene 23:6991–6996PubMedCrossRefGoogle Scholar
  28. Sugiura N, Sakurai K, Hori Y, Karasawa K, Suzuki S, Kimata K (1993) Preparation of lipid-derivatized glycosaminoglycans to probe a regulatory function of the carbohydrate moieties of proteoglycans in cell-matrix interaction. J Biol Chem 268:15779–15787PubMedGoogle Scholar
  29. Sugumaran G, Silbert JE (1988) Sulfation of chondroitin. Specificity, degree of sulfation, and detergent effects with 4-sulfating and 6-sulfating microsomal systems. J Biol Chem 263:4673–4678PubMedGoogle Scholar
  30. Toyama-Sorimachi N, Sorimachi H, Tobita Y, Kitamura F, Yagita H, Suzuki K, Miyasaka M (1995) A novel ligand for CD44 is serglycin, a hematopoietic cell lineage-specific proteoglycan. Possible involvement in lymphoid cell adherence and activation. J Biol Chem 270:7437–7444PubMedCrossRefGoogle Scholar
  31. Uyama T, Ishida M, Izumikawa T, Trybala E, Tufaro F, Bergström T, Sugahara K, Kitagawa H (2006) Chondroitin 4-O-sulfotransferase-1 regulates E disaccharide expression of chondroitin sulfate required for herpes simplex virus infectivity. J Biol Chem 281:38668–38674PubMedCrossRefGoogle Scholar
  32. Wang H, Katagiri Y, McCann TE, Unsworth E, Goldsmith P, Yu ZX, Tan F, Santiago L, Mills EM, Wang Y, Symes AJ, Geller HM (2008) Chondroitin-4-sulfation negatively regulates axonal guidance and growth. J Cell Sci 121(Pt 18):3083–3091PubMedCentralPubMedCrossRefGoogle Scholar
  33. Willis CM, Wrana JL, Klüppel M (2009) Identification and characterization of TGFbeta-dependent and -independent cis-regulatory modules in the C4ST-1/CHST11 locus. Genet Mol Res 8:1331–1343PubMedCrossRefGoogle Scholar
  34. 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 neighboring the acceptor GalNAc residues. Biochem J 384:567–575PubMedCrossRefGoogle Scholar
  35. Yamagata M, Suzuki S, Akiyama SK, Yamada KM, Kimata K (1989) Regulation of cell-substrate adhesion by proteoglycans immobilized on extracellular substrates. J Biol Chem 264:8012–8018PubMedGoogle Scholar
  36. Yamauchi S, Hirahara Y, Usui H, Takeda Y, Hoshino M, Fukuta M, Kimura JH, Habuchi O (1999) Purification and characterization of chondroitin 4-sulfotransferase from the culture medium of a rat chondrosarcoma cell line. J Biol Chem 274:2456–2463PubMedCrossRefGoogle Scholar
  37. Yamauchi S, Mita S, Matsubara T, Fukuta M, Habuchi H, Kimata K, Habuchi O (2000) Molecular cloning and expression of chondroitin 4-sulfotransferase. J Biol Chem 275:8975–8981PubMedCrossRefGoogle Scholar
  38. Yusa A, Kitajima K, Habuchi O (2005) N-linked oligosaccharides are required to produce and stabilize the active form of chondroitin 4-sulphotransferase-1. Biochem J 388:115–121PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Advanced Medical Research CenterAichi Medical UniversityNagakuteJapan

Personalised recommendations