Construction of a human glycogene library and comprehensive functional analysis

Eighteen years have passed after the first mammalian glycosyltransferase was cloned. At the beginning of April, 2001, 110 genes for human glycosyltransferases, including modifying enzymes for carbohydrate chains such as sulfotransferases, had been cloned and analyzed. We started the Glycogene Project (GG project) in April 2001, a comprehensive study on human glycogenes with the aid of bioinformatic technology. The term glycogene includes the genes for glycosyltransferases, sulfotransferases adding sulfate to carbohydrates and sugar-nucleotide transporters, etc. Firstly, as many novel genes, which are the candidates for glycogenes, as possible were searched using bioinformatic technology in databases. They were then cloned and expressed in various expression systems to detect the activity for carbohydrate synthesis. Their substrate specificity was determined using various acceptors. Published in 2004.

[1]  T. Hennet,et al.  Biosynthesis of the Linkage Region of Glycosaminoglycans , 2001, The Journal of Biological Chemistry.

[2]  M. Konishi,et al.  Brain-specific expression of a novel human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T9). , 2000, Biochimica et biophysica acta.

[3]  J. Pevsner,et al.  The expanding β4-galactosyltransferase gene family: messages from the databanks , 1998 .

[4]  M. Hollingsworth,et al.  A family of human beta3-galactosyltransferases. Characterization of four members of a UDP-galactose:beta-N-acetyl-glucosamine/beta-nacetyl-galactosamine beta-1,3-galactosyltransferase family. , 1998, The Journal of biological chemistry.

[5]  H. Narimatsu,et al.  Molecular Cloning and Characterization of a Novel Chondroitin Sulfate Glucuronyltransferase That Transfers Glucuronic Acid toN-Acetylgalactosamine* , 2002, The Journal of Biological Chemistry.

[6]  H. Nakanishi,et al.  Molecular Cloning and Characterization of a Novel UDP-GlcNAc:GalNAc-peptide β1,3-N-Acetylglucosaminyltransferase (β3Gn-T6), an Enzyme Synthesizing the Core 3 Structure of O-Glycans* , 2002, The Journal of Biological Chemistry.

[7]  K. Yamashita,et al.  β1,3‐N‐Acetylglucosaminyltransferase‐7 (β3Gn‐T7) acts efficiently on keratan sulfate‐related glycans , 2004 .

[8]  H. Narimatsu.  Recent Progress in Molecular Cloning of Glycosyltransferase Genes of Eukaryotes , 1994, Microbiology and immunology.

[9]  R. Cummings,et al.  Cloning and Expression of Human Core 1 β1,3-Galactosyltransferase* , 2002, The Journal of Biological Chemistry.

[10]  M. Hollingsworth,et al.  A novel human UDP‐N‐acetyl‐D‐galactosamine:polypeptide N‐acetylgalactosaminyltransferase, GalNAc‐T7, with specificity for partial GalNAc‐glycosylated acceptor substrates , 1999, FEBS letters.

[11]  S. Fujii,et al.  Molecular Cloning and Characterization of Human GnT-IX, a Novel β1,6-N-Acetylglucosaminyltransferase That Is Specifically Expressed in the Brain* , 2003, Journal of Biological Chemistry.

[12]  R. Ueda,et al.  Molecular Cloning and Identification of 3′-Phosphoadenosine 5′-Phosphosulfate Transporter* , 2003, Journal of Biological Chemistry.

[13]  C. Breton,et al.  A new superfamily of protein-O-fucosyltransferases, alpha2-fucosyltransferases, and alpha6-fucosyltransferases: phylogeny and identification of conserved peptide motifs. , 2003, Glycobiology.

[14]  T. Meitinger,et al.  Molecular cloning of a novel human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, GalNAc-T8, and analysis as a candidate autosomal dominant hypophosphatemic rickets (ADHR) gene. , 2000, Gene.

[15]  M. Hollingsworth,et al.  Cloning of a Human UDP-N-Acetyl-α-d-Galactosamine:PolypeptideN-Acetylgalactosaminyltransferase That Complements Other GalNAc-Transferases in Complete O-Glycosylation of the MUC1 Tandem Repeat* , 1998, The Journal of Biological Chemistry.

[16]  Kazuro Furukawa,et al.  Expression Cloning of Human Globoside Synthase cDNAs , 2000, The Journal of Biological Chemistry.

[17]  R. Cummings,et al.  Molecular Cloning and Characterization of a Novel α1,2-Fucosyltransferase (CE2FT-1) from Caenorhabditis elegans * , 2002, The Journal of Biological Chemistry.

[18]  K. Brew,et al.  Cloning and sequencing of cDNA of bovine N-acetylglucosamine (beta 1-4)galactosyltransferase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[19]  H. Kitagawa,et al.  Molecular Cloning and Expression of a Second Chondroitin N-Acetylgalactosaminyltransferase Involved in the Initiation and Elongation of Chondroitin/Dermatan Sulfate* , 2003, The Journal of Biological Chemistry.

[20]  T. Andoh,et al.  Cloning, Expression, and Characterization of a Novel UDP-galactose:β-N-Acetylglucosamine β1,3-Galactosyltransferase (β3Gal-T5) Responsible for Synthesis of Type 1 Chain in Colorectal and Pancreatic Epithelia and Tumor Cells Derived Therefrom* , 1999, The Journal of Biological Chemistry.

[21]  H. Narimatsu,et al.  Initiation of O-Glycan Synthesis in IgA1 Hinge Region Is Determined by a Single Enzyme, UDP-N-Acetyl-α-d-galactosamine:PolypeptideN-Acetylgalactosaminyltransferase 2* , 2003, The Journal of Biological Chemistry.

[22]  H. Narimatsu,et al.  Enzymatic Synthesis of Chondroitin with a Novel Chondroitin Sulfate N-Acetylgalactosaminyltransferase That Transfers N-Acetylgalactosamine to Glucuronic Acid in Initiation and Elongation of Chondroitin Sulfate Synthesis* , 2002, The Journal of Biological Chemistry.

[23]  K. Tachibana,et al.  Characterization of a novel human UDP‐GalNAc transferase, pp‐GalNAc‐T101 , 2002 .

[24]  M. Hollingsworth,et al.  A Family of Human β3-Galactosyltransferases , 1998, The Journal of Biological Chemistry.

[25]  J. Marth,et al.  Novel Sulfated Lymphocyte Homing Receptors and Their Control by a Core1 Extension β1,3-N-Acetylglucosaminyltransferase , 2001, Cell.

[26]  Y. Yamada,et al.  Identification and characterization of three novel beta 1,3-N-acetylglucosaminyltransferases structurally related to the beta 1,3-galactosyltransferase family. , 2001, The Journal of biological chemistry.

[27]  J. Marth,et al.  Cloning and Characterization of a New Human UDP-N-Acetyl-α-d-galactosamine:PolypeptideN-Acetylgalactosaminyltransferase, Designated pp-GalNAc-T13, That Is Specifically Expressed in Neurons and Synthesizes GalNAc α-Serine/Threonine Antigen* , 2003, The Journal of Biological Chemistry.

[28]  K. Tachibana,et al.  Cloning and characterization of a novel UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, pp-GalNAc-T14. , 2003, Biochemical and biophysical research communications.

[29]  Y. Furukawa,et al.  A novel I-branching beta-1,6-N-acetylglucosaminyltransferase involved in human blood group I antigen expression. , 2003, Blood.

[30]  M. Shionyu,et al.  Chondroitin Sulfate Synthase-2 , 2003, Journal of Biological Chemistry.

[31]  岡島 徹也.  Human homolog of caenorhabditis elegans sqv-3 gene is galactosyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans , 2000 .

[32]  H. Narimatsu,et al.  Characterization of a Heparan Sulfate 3-O-Sulfotransferase-5, an Enzyme Synthesizing a Tetrasulfated Disaccharide* , 2003, Journal of Biological Chemistry.

[33]  H. Kitagawa,et al.  Molecular cloning and expression of human chondroitin N-acetylgalactosaminyltransferase: the key enzyme for chain initiation and elongation of chondroitin/dermatan sulfate on the protein linkage region tetrasaccharide shared by heparin/heparan sulfate. , 2002, The Journal of biological chemistry.

[34]  M. Kaneko,et al.  A novel β(1,6)‐N‐acetylglucosaminyltransferase V (GnT‐VB) 1 , 2003 .

[35]  E. Bennett,et al.  Cloning and Expression of a Proteoglycan UDP-Galactose:β-Xylose β1,4-Galactosyltransferase I , 1999, The Journal of Biological Chemistry.

[36]  S. Fujii,et al.  N-Acetylglucosaminyltransferase IX Acts on the GlcNAcβ1,2-Manα1-Ser/Thr Moiety, Forming a 2,6-Branched Structure in Brain O-Mannosyl Glycan* , 2004, Journal of Biological Chemistry.

[37]  A. V. van Kessel,et al.  A Family of Human β4-Galactosyltransferases , 1997, The Journal of Biological Chemistry.

[38]  H. Narimatsu,et al.  Molecular Cloning and Characterization of a Human Multisubstrate Specific Nucleotide-sugar Transporter Homologous to Drosophila fringe connection* , 2004, Journal of Biological Chemistry.

[39]  Charles Elkan,et al.  Fitting a Mixture Model By Expectation Maximization To Discover Motifs In Biopolymer , 1994, ISMB.

[40]  F. Homa,et al.  Isolation and expression of a cDNA clone encoding a bovine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase. , 1993, The Journal of biological chemistry.

[41]  H. Kitagawa,et al.  Molecular Cloning of a Chondroitin Polymerizing Factor That Cooperates with Chondroitin Synthase for Chondroitin Polymerization* , 2003, Journal of Biological Chemistry.

[42]  E. Bennett,et al.  Cloning of a novel member of the UDP-galactose:beta-N-acetylglucosamine beta1,4-galactosyltransferase family, beta4Gal-T4, involved in glycosphingolipid biosynthesis. , 1998, The Journal of biological chemistry.

[43]  K. Tachibana,et al.  Characterization of a novel human UDP‐GalNAc transferase, pp‐GalNAc‐T15 , 2004, FEBS letters.

[44]  H. Narimatsu,et al.  Molecular Cloning and Characterization of a Novel UDP-Gal:GalNAcα Peptide β1,3-Galactosyltransferase (C1Gal-T2), an Enzyme Synthesizing a Core 1 Structure of O-Glycan* , 2002, The Journal of Biological Chemistry.

[45]  E. Bennett,et al.  Purification and cDNA Cloning of a Human UDP-N-acetyl-α- D-galactosamine:polypeptide N-Acetylgalactosaminyltransferase (*) , 1995, The Journal of Biological Chemistry.

[46]  K. Sasaki,et al.  Identification and Characterization of Three Novel β1,3-N-Acetylglucosaminyltransferases Structurally Related to the β1,3-Galactosyltransferase Family* , 2001, The Journal of Biological Chemistry.

[47]  H. Nakanishi,et al.  Molecular cloning and characterization of a novel human beta 1,4-N-acetylgalactosaminyltransferase, beta 4GalNAc-T3, responsible for the synthesis of N,N'-diacetyllactosediamine, galNAc beta 1-4GlcNAc. , 2003, Journal of Biological Chemistry.

[48]  H. Kitagawa,et al.  Molecular Cloning and Expression of a Human Chondroitin Synthase* , 2001, The Journal of Biological Chemistry.

[49]  R. Cummings,et al.  Molecular Cloning and Enzymatic Characterization of a UDP-GalNAc:GlcNAcβ-R β1,4-N-Acetylgalactosaminyltransferase fromCaenorhabditis elegans * , 2002, The Journal of Biological Chemistry.

[50]  Peter Roepstorff,et al.  Functional Conservation of Subfamilies of Putative UDP-N-acetylgalactosamine:Polypeptide N-Acetylgalactosaminyltransferases inDrosophila, Caenorhabditis elegans, and Mammals , 2002, The Journal of Biological Chemistry.

[51]  H. Nakanishi,et al.  Molecular cloning and characterization of β1,4‐N‐acetylgalactosaminyltransferases IV synthesizing N,N′‐diacetyllactosediamine1 , 2004 .

[52]  H. Narimatsu,et al.  Comparison of glycosyltransferase families using the profile hidden Markov model. , 2003, Biochemical and biophysical research communications.

[53]  I. Kirsch,et al.  Bovine galactosyltransferase: identification of a clone by direct immunological screening of a cDNA expression library. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[54]  H. Nakanishi,et al.  Molecular Cloning and Characterization of a Novel Human β1,4-N-Acetylgalactosaminyltransferase, β4GalNAc-T3, Responsible for the Synthesis of N,N′-Diacetyllactosediamine, GalNAcβ1–4GlcNAc* , 2003, Journal of Biological Chemistry.

[55]  R. Cummings,et al.  Cloning and expression of human core 1 beta1,3-galactosyltransferase. , 2002, The Journal of biological chemistry.

[56]  H. Narimatsu,et al.  Chondroitin Sulfate Synthase-3 , 2003, Journal of Biological Chemistry.

[57]  E. Berger,et al.  Genomic Cloning and Expression of Three Murine UDP-galactose: β-N-Acetylglucosamine β1,3-Galactosyltransferase Genes* , 1998, The Journal of Biological Chemistry.

[58]  E. Bennett,et al.  cDNA cloning and expression of a novel human UDP-N-acetyl-alpha-D-galactosamine. Polypeptide N-acetylgalactosaminyltransferase, GalNAc-t3. , 1996, The Journal of biological chemistry.

[59]  T. Imamura,et al.  Differential roles of two N-acetylgalactosaminyltransferases, CSGalNAcT-1, and a novel enzyme, CSGalNAcT-2. Initiation and elongation in synthesis of chondroitin sulfate. , 2003, The Journal of biological chemistry.

[60]  T. Irimura,et al.  Molecular Cloning and Characterization of UDP-GlcNAc:Lactosylceramide β1,3-N-Acetylglucosaminyltransferase (β3Gn-T5), an Essential Enzyme for the Expression of HNK-1 and Lewis X Epitopes on Glycolipids* , 2001, The Journal of Biological Chemistry.

[61]  J. van den Born,et al.  Antibody-based assay for N-deacetylase activity of heparan sulfate/heparin N-deacetylase/N-sulfotransferase (NDST): novel characteristics of NDST-1 and -2. , 2003, Glycobiology.

[62]  Kazuro Furukawa,et al.  Expression Cloning of Rat cDNA Encoding UDP-galactose:GD2 β1,3-galactosyltransferase That Determines the Expression of GD1b/GM1/GA1 * , 1997, The Journal of Biological Chemistry.

[63]  E. Berger,et al.  A β-1,3-N-acetylglucosaminyltransferase with poly-N-acetyllactosamine synthase activity is structurally related to β-1,3-galactosyltransferases , 1999 .

[64]  H. Clausen,et al.  Identification and characterization of large galactosyltransferase gene families: galactosyltransferases for all functions. , 1999, Biochimica et biophysica acta.

[65]  M. Hollingsworth,et al.  Cloning and Characterization of a Close Homologue of Human UDP-N-acetyl-α-d-galactosamine:Polypeptide N-Acetylgalactosaminyltransferase-T3, Designated GalNAc-T6 , 1999, The Journal of Biological Chemistry.

[66]  R. Cummings,et al.  A unique molecular chaperone Cosmc required for activity of the mammalian core 1 β3-galactosyltransferase , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[67]  E. Berger,et al.  The β1,3-Galactosyltransferase β3GalT-V Is a Stage-specific Embryonic Antigen-3 (SSEA-3) Synthase* , 2000, The Journal of Biological Chemistry.

[68]  K. Tachibana,et al.  Molecular cloning and characterization of a novel member of the UDP‐GalNAc:polypeptide N‐acetylgalactosaminyltransferase family, pp‐GalNAc‐T12 1 , 2002 .

[69]  K. Tachibana,et al.  Molecular cloning and characterization of a novel member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family, pp-GalNAc-T12. , 2002, FEBS letters.

[70]  J. Paulson,et al.  Glycosyltransferases. Structure, localization, and control of cell type-specific glycosylation. , 1989, The Journal of biological chemistry.