KEGG   PATHWAY: pdic00532
Entry
pdic00532                   Pathway                                
Name
Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate - Phyllostomus discolor (pale spear-nosed bat)
Description
Glycosaminoglycans (GAGs) are linear polysaccharide chains consisting of repeating disaccharide units and form proteglycans by covalently attaching to their core proteins. Chondroitin sulfate (CS) is a glycosaminoglycan with the disaccharide unit of beta-D-galactosamine (GalNAc) and beta-D-glucuronic acid (GlcA), and often modified with ester-linked sulfate at certain positions. Dermatan sulfate (DS) is a modified form of CS, in which a portion of D-glucuronate residues is epimerized to L-iduronates (IdoA). CS and DS are linked to serine residues in core proteins via a linkage tetrasaccharide formed by the transfer of xylose and three more residues [MD:M00057]. The assembly process of CS is initiated by transferring GalNAc residue to the linkage tetrasaccharide. The polymerization is catalyzed by bifunctional enzymes (chondroitin synthases) possessing both beta 1,3 glucuronosyltransferase and beta 1,4 N-acetylgalactosaminyltransferase activities [MD:M00058]. Chondroitin polymerization also requires the action of the chondroitin polymerizing factor. There are various O-sulfation patterns in CS and DS, where 4-O sulfation and 6-O sulfation of GalNAc and 2-O-sulfation of the uronic acids (GlcA / IdoA) are mainly found.
Class
Metabolism; Glycan biosynthesis and metabolism
Pathway map
pdic00532  Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate
pdic00532

Module
pdic_M00057  Glycosaminoglycan biosynthesis, linkage tetrasaccharide [PATH:pdic00532]
pdic_M00058  Glycosaminoglycan biosynthesis, chondroitin sulfate backbone [PATH:pdic00532]
Other DBs
GO: 0030206 0030208
Organism
Phyllostomus discolor (pale spear-nosed bat) [GN:pdic]
Gene
114509707  XYLT1; xylosyltransferase 1 isoform X1 [KO:K00771] [EC:2.4.2.26]
114502779  XYLT2; xylosyltransferase 2 [KO:K00771] [EC:2.4.2.26]
114510363  beta-1,4-galactosyltransferase 7-like [KO:K00733] [EC:2.4.1.133]
114510143  B4GALT7; beta-1,4-galactosyltransferase 7 isoform X3 [KO:K00733] [EC:2.4.1.133]
114497174  B3GALT6; beta-1,3-galactosyltransferase 6 [KO:K00734] [EC:2.4.1.134]
114499679  B3GAT3; galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3 [KO:K10158] [EC:2.4.1.135]
114497160  CSGALNACT2; LOW QUALITY PROTEIN: chondroitin sulfate N-acetylgalactosaminyltransferase 2 [KO:K00746] [EC:2.4.1.174 2.4.1.175]
114508884  CSGALNACT1; chondroitin sulfate N-acetylgalactosaminyltransferase 1 [KO:K00746] [EC:2.4.1.174 2.4.1.175]
114510434  CHSY3; chondroitin sulfate synthase 3 [KO:K13499] [EC:2.4.1.175 2.4.1.226]
114488646  CHSY1; chondroitin sulfate synthase 1 [KO:K13499] [EC:2.4.1.175 2.4.1.226]
114494176  CHPF; chondroitin sulfate synthase 2 [KO:K00747] [EC:2.4.1.175 2.4.1.226]
114508107  CHPF2; chondroitin sulfate glucuronyltransferase [KO:K03419] [EC:2.4.1.226]
114494200  DSE; dermatan-sulfate epimerase isoform X1 [KO:K01794] [EC:5.1.3.19]
114506901  DSEL; dermatan-sulfate epimerase-like protein [KO:K01794] [EC:5.1.3.19]
114513082  CHST11; carbohydrate sulfotransferase 11 isoform X1 [KO:K01017] [EC:2.8.2.5]
114509728  CHST12; carbohydrate sulfotransferase 12 [KO:K04742] [EC:2.8.2.5]
114506029  CHST13; carbohydrate sulfotransferase 13 [KO:K07779] [EC:2.8.2.5]
114496655  CHST3; carbohydrate sulfotransferase 3 isoform X1 [KO:K01020] [EC:2.8.2.17]
114505183  CHST7; carbohydrate sulfotransferase 7 [KO:K04743] [EC:2.8.2.17]
114497466  CHST15; carbohydrate sulfotransferase 15 [KO:K08106] [EC:2.8.2.33]
114495199  UST; uronyl 2-sulfotransferase isoform X2 [KO:K03193] [EC:2.8.2.-]
114491774  CHST14; carbohydrate sulfotransferase 14 [KO:K08105] [EC:2.8.2.35]
Compound
C00053  3'-Phosphoadenylyl sulfate
C00054  Adenosine 3',5'-bisphosphate
C00401  Chondroitin
C01490  Dermatan
C02189  [Protein]-L-serine
G00154   
G00155   
G00156   
G00157   
G00158   
G00159   
G00160   
Reference
  Authors
Sugahara K, Kitagawa H.
  Title
Recent advances in the study of the biosynthesis and functions of sulfated glycosaminoglycans.
  Journal
Curr Opin Struct Biol 10:518-27 (2000)
DOI:10.1016/S0959-440X(00)00125-1
Reference
  Authors
Li JP, Gong F, El Darwish K, Jalkanen M, Lindahl U.
  Title
Characterization of the D-glucuronyl C5-epimerase involved in the biosynthesis of heparin and heparan sulfate.
  Journal
J Biol Chem 276:20069-77 (2001)
DOI:10.1074/jbc.M011783200
Reference
  Authors
Gotting C, Kuhn J, Zahn R, Brinkmann T, Kleesiek K
  Title
Molecular cloning and expression of human UDP-d-Xylose:proteoglycan core protein beta-d-xylosyltransferase and its first isoform XT-II.
  Journal
J Mol Biol 304:517-28 (2000)
DOI:10.1006/jmbi.2000.4261
Reference
  Authors
Almeida R, Levery SB, Mandel U, Kresse H, Schwientek T, Bennett EP, Clausen H
  Title
Cloning and expression of a proteoglycan UDP-galactose:beta-xylose beta1,4-galactosyltransferase I. A seventh member of the human beta4-galactosyltransferase gene family.
  Journal
J Biol Chem 274:26165-71 (1999)
DOI:10.1074/jbc.274.37.26165
Reference
  Authors
Bai X, Zhou D, Brown JR, Crawford BE, Hennet T, Esko JD
  Title
Biosynthesis of the linkage region of glycosaminoglycans: cloning and activity of galactosyltransferase II, the sixth member of the beta 1,3-galactosyltransferase family (beta 3GalT6).
  Journal
J Biol Chem 276:48189-95 (2001)
DOI:10.1074/jbc.M107339200
Reference
PMID:9506957
  Authors
Kitagawa H, Tone Y, Tamura J, Neumann KW, Ogawa T, Oka S, Kawasaki T, Sugahara K
  Title
Molecular cloning and expression of glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans.
  Journal
J Biol Chem 273:6615-8 (1998)
DOI:10.1074/jbc.273.12.6615
Reference
  Authors
Silbert JE, Sugumaran G
  Title
Biosynthesis of chondroitin/dermatan sulfate.
  Journal
IUBMB Life 54:177-86 (2002)
DOI:10.1080/15216540214923
Reference
  Authors
Izumikawa T, Uyama T, Okuura Y, Sugahara K, Kitagawa H
  Title
Involvement of chondroitin sulfate synthase-3 (chondroitin synthase-2) in chondroitin polymerization through its interaction with chondroitin synthase-1 or chondroitin-polymerizing factor.
  Journal
Biochem J 403:545-52 (2007)
DOI:10.1042/BJ20061876
Reference
  Authors
Kitagawa H, Izumikawa T, Uyama T, Sugahara K
  Title
Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization.
  Journal
J Biol Chem 278:23666-71 (2003)
DOI:10.1074/jbc.M302493200
Reference
  Authors
Izumikawa T, Okuura Y, Koike T, Sakoda N, Kitagawa H
  Title
Chondroitin 4-O-sulfotransferase-1 regulates the chain length of chondroitin sulfate in co-operation with chondroitin N-acetylgalactosaminyltransferase-2.
  Journal
Biochem J 434:321-31 (2011)
DOI:10.1042/BJ20101456
Reference
  Authors
Malmstrom A, Bartolini B, Thelin MA, Pacheco B, Maccarana M
  Title
Iduronic Acid in chondroitin/dermatan sulfate: biosynthesis and biological function.
  Journal
J Histochem Cytochem 60:916-25 (2012)
DOI:10.1369/0022155412459857
Reference
  Authors
Sugahara K, Mikami T
  Title
Chondroitin/dermatan sulfate in the central nervous system.
  Journal
Curr Opin Struct Biol 17:536-45 (2007)
DOI:10.1016/j.sbi.2007.08.015
Reference
  Authors
Kusche-Gullberg M, Kjellen L
  Title
Sulfotransferases in glycosaminoglycan biosynthesis.
  Journal
Curr Opin Struct Biol 13:605-11 (2003)
DOI:10.1016/j.sbi.2003.08.002
Reference
  Authors
Pacheco B, Maccarana M, Malmstrom A
  Title
Dermatan 4-O-sulfotransferase 1 is pivotal in the formation of iduronic acid blocks in dermatan sulfate.
  Journal
Glycobiology 19:1197-203 (2009)
DOI:10.1093/glycob/cwp110
Reference
  Authors
Prabhakar V, Sasisekharan R
  Title
The biosynthesis and catabolism of galactosaminoglycans.
  Journal
Adv Pharmacol 53:69-115 (2006)
DOI:10.1016/S1054-3589(05)53005-9
Reference
  Authors
Mikami T, Mizumoto S, Kago N, Kitagawa H, Sugahara K
  Title
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.
  Journal
J Biol Chem 278:36115-27 (2003)
DOI:10.1074/jbc.M306044200
Related
pathway
pdic00531  Glycosaminoglycan degradation
KO pathway
ko00532   
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