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Beta-1,3-Glucuronyltransferase 3 (Glucuronosyltransferase I) (B3GAT3)

  • Hiroshi Kitagawa
  • Satomi Nadanaka
Reference work entry

Abstract

β-1,3-glucuronyltransferase 3 (glucuronosyltransferase I: GlcAT-I) transfers GlcA from UDP-GlcA to the trisaccharide-serine, Galβ1-3Galβ1-4Xylβ1-O-Ser, to form the glycosaminoglycan (GAG)-protein linkage region, GlcAβ1-3Galβ1-3Galβ1-4Xylβ1-O-Ser, common to various proteoglycans. GlcAT-I comprises 335 amino acids and one N-glycan; it has a type II transmembrane orientation characteristic of many other glycosyltransferases (Kitagawa et al. 1998; Wei et al. 1999). The molecular mass of the GlcAT-I peptide backbone is 37 kDa, but the mass of the mature protein increases with glycosylation to around 47 kDa. Another characteristic feature in the amino acid sequence of GlcAT-I is a proline-rich domain (from Pro-30 to Pro-75) next to the transmembrane region; this juxtaposition occurs in several other glycosyltransferases including glucuronyltransferase-P (GlcAT-P) and glucuronyltransferase-D (GlcAT-D), which synthesize the precursor structure GlcAβ1-3Galβ1-4GlcNAc-R for the HNK-1 carbohydrate epitope GlcA(3-O-sulfate)β1-3Galβ1-4GlcNAc-R (Seiki et al. 1999; Shimoda et al. 1999; Terayama et al. 1997). Database searches indicate that the amino acid sequence of GlcAT-I is 43-46 % identical to GlcAT-P and GlcAT-D, respectively. The highest sequence identity is found in the COOH-terminal catalytic domain of each GlcAT. The catalytic domain of GlcAT-I is positioned immediately C-terminal to the proline-rich domain and stretches for 252 amino acids from Pro-68 to Glu-319; this domain has about 60 % identity with the catalytic domains from other GlcAT (Kitagawa et al. 1998; Wei et al. 1999), and the domain contains the four previously identified, highly conserved motifs (I–IV) found in putative GlcAT from different animal species (Shimoda et al. 1999; Terayama et al. 1997).

Keywords

Chondroitin Sulfate Nucleus Pulposus Cell Joint Dislocation Acceptor Substrate Repeat Disaccharide Unit 
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.

References

  1. Almeida R, Levery SB, Mandel U, Kresse H, Schwientek T, Bennett EP, Clausen H (1999) Cloning and expression of a proteoglycan UDP-galactose:beta-xylose beta1,4-galactosyltransferase I. A seventh member of the human beta4-galactosyltransferase gene family. J Biol Chem 274:26165–26171PubMedCrossRefGoogle Scholar
  2. Baasanjav S, Al-Gazali L, Hashiguchi T, Mizumoto S, Fischer B, Horn D, Seelow D, Ali BR, Aziz SA, Langer R, Saleh AA, Becker C, Nurnberg G, Cantagrel V, Gleeson JG, Gomez D, Michel JB, Stricker S, Lindner TH, Nurnberg P, Sugahara K, Mundlos S, Hoffmann K (2011) Faulty initiation of proteoglycan synthesis causes cardiac and joint defects. Am J Hum Genet 89:15–27PubMedCentralPubMedCrossRefGoogle Scholar
  3. Bai X, Wei G, Sinha A, Esko JD (1999) Chinese hamster ovary cell mutants defective in glycosaminoglycan assembly and glucuronosyltransferase I. J Biol Chem 274:13017–13024PubMedCrossRefGoogle Scholar
  4. Bakker H, Friedmann I, Oka S, Kawasaki T, Nifant’ev N, Schachner M, Mantei N (1997) Expression cloning of a cDNA encoding a sulfotransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope. J Biol Chem 272:29942–29946PubMedCrossRefGoogle Scholar
  5. Barre L, Venkatesan N, Magdalou J, Netter P, Fournel-Gigleux S, Ouzzine M (2006) Evidence of calcium-dependent pathway in the regulation of human beta1,3-glucuronosyltransferase-1 (GlcAT-I) gene expression: a key enzyme in proteoglycan synthesis. FASEB J 20:1692–1694PubMedCrossRefGoogle Scholar
  6. Brandt AE, Distler J, Jourdian GW (1969) Biosynthesis of the chondroitin sulfate-protein linkage region: purification and properties of a glucuronosyltransferase from embryonic chick brain. Proc Natl Acad Sci USA 64:374–380PubMedCrossRefGoogle Scholar
  7. Curenton T, Ekborg G, Roden L (1991) Glucuronosyl transfer to galactose residues in the biosynthesis of HNK-1 antigens and xylose-containing glycosaminoglycans: one or two transferases? Biochem Biophys Res Commun 179:416–422.PubMedCrossRefGoogle Scholar
  8. Fondeur-Gelinotte M, Lattard V, Oriol R, Mollicone R, Jacquinet JC, Mulliert G, Gulberti S, Netter P, Magdalou J, Ouzzine M, Fournel-Gigleux S (2006) Phylogenetic and mutational analyses reveal key residues for UDP-glucuronic acid binding and activity of beta1,3-glucuronosyltransferase I (GlcAT-I). Protein Sci 15:1667–1678PubMedCrossRefGoogle Scholar
  9. Fondeur-Gelinotte M, Lattard V, Gulberti S, Oriol R, Mulliert G, Coughtrie MW, Magdalou J, Netter P, Ouzzine M, Fournel-Gigleux S (2007) Molecular basis for acceptor substrate specificity of the human beta1,3-glucuronosyltransferases GlcAT-I and GlcAT-P involved in glycosaminoglycan and HNK-1 carbohydrate epitope biosynthesis, respectively. Glycobiology 17:857–867PubMedCrossRefGoogle Scholar
  10. Gouze JN, Bordji K, Gulberti S, Terlain B, Netter P, Magdalou J, Fournel-Gigleux S, Ouzzine M (2001) Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. Arthritis Rheum 44:351–360PubMedCrossRefGoogle Scholar
  11. Gulberti S, Fournel-Gigleux S, Mulliert G, Aubry A, Netter P, Magdalou J, Ouzzine M (2003) The functional glycosyltransferase signature sequence of the human beta 1,3-glucuronosyltransferase is a XDD motif. J Biol Chem 278:32219–32226PubMedCrossRefGoogle Scholar
  12. Helting T (1972) Biosynthesis of heparin. Solubilization and partial purification of uridine diphosphate glucuronic acid: acceptor glucuronosyltransferase from mouse mastocytoma. J Biol Chem 247:4327–4332PubMedGoogle Scholar
  13. Helting T, Roden L (1969) Biosynthesis of chondroitin sulfate. II. Glucuronosyl transfer in the formation of the carbohydrate-protein linkage region. J Biol Chem 244:2799–2805PubMedGoogle Scholar
  14. Herman T, Horvitz HR (1999) Three proteins involved in Caenorhabditis elegans vulval invagination are similar to components of a glycosylation pathway. Proc Natl Acad Sci USA 96:974–979PubMedCrossRefGoogle Scholar
  15. Hiyama A, Gajghate S, Sakai D, Mochida J, Shapiro IM, Risbud MV (2009) Activation of TonEBP by calcium controls {beta}1,3-glucuronosyltransferase-I expression, a key regulator of glycosaminoglycan synthesis in cells of the intervertebral disc. J Biol Chem 284:9824–9834PubMedCrossRefGoogle Scholar
  16. Izumikawa T, Kitagawa H (2010) Mice deficient in glucuronyltransferase-I. Prog Mol Biol Transl Sci 93:19–34PubMedCrossRefGoogle Scholar
  17. Izumikawa T, Kanagawa N, Watamoto Y, Okada M, Saeki M, Sakano M, Sugahara K, Sugihara K, Asano M, Kitagawa H (2010) Impairment of embryonic cell division and glycosaminoglycan biosynthesis in glucuronyltransferase-I-deficient mice. J Biol Chem 285:12190–12196PubMedCrossRefGoogle Scholar
  18. Kitagawa H, Ujikawa M, Tsutsumi K, Tamura J, Neumann KW, Ogawa T, Sugahara K (1997) Characterization of serum beta-glucuronyltransferase involved in chondroitin sulfate biosynthesis. Glycobiology 7:905–911PubMedCrossRefGoogle Scholar
  19. Kitagawa H, Tone Y, Tamura J, Neumann KW, Ogawa T, Oka S, Kawasaki T, Sugahara K (1998) Molecular cloning and expression of glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans. J Biol Chem 273:6615–6618PubMedCrossRefGoogle Scholar
  20. Kitagawa H, Taoka M, Tone Y, Sugahara K (2001) Human glycosaminoglycan glucuronyltransferase I gene and a related processed pseudogene: genomic structure, chromosomal mapping and characterization. Biochem J 358:539–546PubMedCrossRefGoogle Scholar
  21. Ong E, Yeh JC, Ding Y, Hindsgaul O, Fukuda M (1998) Expression cloning of a human sulfotransferase that directs the synthesis of the HNK-1 glycan on the neural cell adhesion molecule and glycolipids. J Biol Chem 273:5190–5195PubMedCrossRefGoogle Scholar
  22. Ouzzine M, Gulberti S, Netter P, Magdalou J, Fournel-Gigleux S (2000) Structure/function of the human Ga1beta1,3-glucuronosyltransferase. Dimerization and functional activity are mediated by two crucial cysteine residues. J Biol Chem 275:28254–28260PubMedGoogle Scholar
  23. Ouzzine M, Gulberti S, Levoin N, Netter P, Magdalou J, Fournel-Gigleux S (2002) The donor substrate specificity of the human beta 1,3-glucuronosyltransferase I toward UDP-glucuronic acid is determined by two crucial histidine and arginine residues. J Biol Chem 277:25439–25445PubMedCrossRefGoogle Scholar
  24. Ouzzine M, Venkatesan N, Fournel-Gigleux S (2012) Proteoglycans and cartilage repair. Methods Mol Biol 836:339–355PubMedCrossRefGoogle Scholar
  25. Pedersen LC, Tsuchida K, Kitagawa H, Sugahara K, Darden TA, Negishi M (2000) Heparan/chondroitin sulfate biosynthesis. Structure and mechanism of human glucuronyltransferase I. J Biol Chem 275:34580–34585PubMedCrossRefGoogle Scholar
  26. Pedersen LC, Darden TA, Negishi M (2002) Crystal structure of beta 1,3-glucuronyltransferase I in complex with active donor substrate UDP-GlcUA. J Biol Chem 277:21869–21873PubMedCrossRefGoogle Scholar
  27. Schwarting GA, Jungalwala FB, Chou DK, Boyer AM, Yamamoto M (1987) Sulfated glucuronic acid-containing glycoconjugates are temporally and spatially regulated antigens in the developing mammalian nervous system. Dev Biol 120:65–76PubMedCrossRefGoogle Scholar
  28. Seiki T, Oka S, Terayama K, Imiya K, Kawasaki T (1999) Molecular cloning and expression of a second glucuronyltransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope. Biochem Biophys Res Commun 255:182–187PubMedCrossRefGoogle Scholar
  29. Shimoda Y, Tajima Y, Nagase T, Harii K, Osumi N, Sanai Y (1999) Cloning and expression of a novel galactoside beta1, 3-glucuronyltransferase involved in the biosynthesis of HNK-1 epitope. J Biol Chem 274:17115–17122PubMedCrossRefGoogle Scholar
  30. Terayama K, Oka S, Seiki T, Miki Y, Nakamura A, Kozutsumi Y, Takio K, Kawasaki T (1997) Cloning and functional expression of a novel glucuronyltransferase involved in the biosynthesis of the carbohydrate epitope HNK-1. Proc Natl Acad Sci USA 94:6093–6098PubMedCrossRefGoogle Scholar
  31. Tone Y, Kitagawa H, Imiya K, Oka S, Kawasaki T, Sugahara K (1999) Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans. FEBS Lett 459:415–420PubMedCrossRefGoogle Scholar
  32. Tone Y, Pedersen LC, Yamamoto T, Izumikawa T, Kitagawa H, Nishihara J, Tamura J, Negishi M, Sugahara K (2008) 2-o-phosphorylation of xylose and 6-o-sulfation of galactose in the protein linkage region of glycosaminoglycans influence the glucuronyltransferase-I activity involved in the linkage region synthesis. J Biol Chem 283:16801–16807PubMedCrossRefGoogle Scholar
  33. Tsuji S (1996) Molecular cloning and functional analysis of sialyltransferases. J Biochem 120:1–13PubMedCrossRefGoogle Scholar
  34. Venkatesan N, Barre L, Benani A, Netter P, Magdalou J, Fournel-Gigleux S, Ouzzine M (2004) Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: a strategy to promote cartilage repair. Proc Natl Acad Sci USA 101:18087–18092PubMedCrossRefGoogle Scholar
  35. Venkatesan N, Ouzzine M, Kolb M, Netter P, Ludwig MS (2011) Increased deposition of chondroitin/dermatan sulfate glycosaminoglycan and upregulation of beta1,3-glucuronosyltransferase I in pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 300:L191–L203PubMedCrossRefGoogle Scholar
  36. Wei G, Bai X, Sarkar AK, Esko JD (1999) Formation of HNK-1 determinants and the glycosaminoglycan tetrasaccharide linkage region by UDP-GlcUA: Galactose beta1, 3-glucuronosyltransferases. J Biol Chem 274:7857–7864PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Department of BiochemistryKobe Pharmaceutical UniversityHigashinada-kuJapan

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