Table Of ContentSSpprriinnggeerr Japan KK
Tokyo
Berlin
Heidelberg
New York
Hong Kong
London
Milan
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Handbook of Glycosyltransferases
and Related Genes
Edited by:
Naoyuki Taniguchi, Koichi Honke, Minoru Fukuda
Co-editors:
Henrik Clausen James W. Dennis
Kiyoshi Furukawa Koichi Furukawa
Gerald W. Hart Yoshio Hirabayashi
Reiji Kannagi Masao Kawakita
Toshisuke Kawasaki Koji Kimata
Taroh Kinoshita Ulf Lindahl
Takashi Muramatsu Hisashi N arimatsu
Masaki Saito Harry Schachter
Joel H. Shaper Pamela Stanley
KazuyukiSugahara Akemi Suzuki
Lawrence A. Tabak Shuichi Tsuji
Dirk H. Van den Eijnden Katsuko Yamashita
Masaki Yanagishita
With 95 Figures, Including 5 in Color
Springer
NAOYUKI TANIGUCHI, M.D., Ph.D.
NPrAoOfeYsUsKorI, TDAeNpIaGrUtmCeHnI,t Mof.D B.,i oPchh.Dem. istry
POrsoafkeass Uorn, iDveerpsaitryt mMeendti coafl BSicohcohoelm istry
2O-s2a Ykaa mUandivaoerksai,t yS uMitead, iOcasla kSac h5o6o5l- 0871, Japan
2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
KOICHI HONKE, M.D., Ph.D.
KAasrsCocHiIa tHe OPNroKfEe,s sMor.D, D., ePpha.Drt.m ent of Biochemistry
AOsssaokcai aUten iPvreorfseistyso Mr, eDdiecpaal rStmcheonotl o f Biochemistry
O2-s2a Ykaa mUandivaeorksai,t yS uMitead, iOcasla kSac h5o6o5l- 0871, Japan
2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
MINORU FUKUDA, Ph.D.
MPrIoNfOesRsUo rF, UGKlyUcDoAbi, oPlho.gDy. Program
PCraonfceessro Rr,e Gselayrccohb iIonlsotgityu tPer ogram
CThane cBeru rRnehsaemar cIhn sItnitsutitteu te
T10h9e0 1B uNronrhtahm T oInrrsetiyt uPtien es Road, La Jolla, CA 92037, USA
10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Cover Illustration by Koichi Honke
Cover Illustration by Koichi Honke
ISBN 978-4-431-67996-7
ISBN 4-431-70311-X Springer-Verlag Tokyo Berlin Heidelberg New York
Library of Congress Cataloging-in-Publication Data
HLiabnrdarbyo oofk Coof ngglyrecsoss yCltartaanlosfgeirnags-eisn -aPnudb lrieclaattieodn gDenaetas / N. Taniguchi, K. Honke, M. Fukuda, eds.
Handbopo.k;c omf .g lycosyltransferases and related genes / N. Taniguchi, K. Honke, M. Fukuda, eds.
Incpl.u;dcems .b ibliographical references.
IInScBluNd e9s7 8b-ib4l-i4o3g1r-a6p7h9ic9a6l- 7re ferencIeSs.B N 978-4-431-67877-9 (eBook)
IDSOBNI 1404.311070073/1917X8 -(4h-a4r3d1c-o6v7e8r7: 7a-l9k . paper)
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Preface
The so-called postgenomic research era has now been launched, and the field of gly
cobiology and glycotechnology has become one of the most important areas in life
science because glycosylation is the most common post-translational modification
reaction of proteins in vivo. On the basis of Swiss-Prot data, over 50% proteins are
known to undergo glycosylation, but in fact the actual functions of most of the sugar
chains in the glycoconjugates remain unknown.
The complex carbohydrate chains of glycoproteins, glycolipids, and proteoglycans
represent the secondary gene products formed through the reactions of glycosyl
transferases. The regulation of the biosynthesis of sugar chains is under the control
of the expression of glycosyltransferases, their substrate specificity, and their local
ization in specific tissue sites. There is a growing body of evidence to suggest that
these enzymes play pivotal roles in a variety of important cellular differentiation and
developmental events, as well as in disease processes. Over 300 glycosyltransferases
appear to exist in mammalian tissues. If the genes that have been purified and cloned
from various species such as humans, cattle, pigs, rats and mice are counted as one,
approximately 110 glycogenes that encode glycosyltransferases and related genes have
been cloned at present, and this number continues to grow each day. However, most
of the functions of the glycosyltransferase genes and related genes are unknown. This
fact has stimulated numerous new and interesting approaches in molecular biologi
cal investigations.
The removal of a specific glycogene in knockout mice indicates that some of the
glycosyltransferases are essential for survival, development, and oncogenesis. Exper
iments using cells or animals that had been transfected with a specific glycosyltrans
ferase gene show that these enzymes relate to cancer metastases, cellular invasion, and
the suppression of xenoantigen expression. Although a number of excellent investi
gations have been conducted, the issue of the real functions of glycoconjugates of
interest remains to be elucidated. The reason for the difficulty in exploring the func
tional significance of glycosyltransferase genes, or glycogenes, is that even if we are
able to disrupt the gene and obtain phenotypic changes in mice, we cannot explain
this as a consequence or a cause of disease. Moreover, and more importantly, we
cannot identify the actual target protein(s) in vivo that may be affected by the lack of
sugar chains. The phenotypic changes observed are actually not due to a disrupted
glycogene but, rather, to the secondary effect of the glycogene which may affect the
v
VI Preface
aberrant glycosylation of other glycoproteins. The same would be true for transgenic
mice that overexpress specified glycogenes or for Congenital Disorders of Glycosyla
tion (CGD) patients with various symptoms that cannot be explained via the mecha
nism by which the symptoms appeared. In the future, therefore, the identification of
target proteins in patients or in glycogene-disrupted animals is a prerequisite for
understanding the real cause of the pathophysiology of diseases. The field of func
tional glycomics focuses on carrying out this type of research. This handbook is useful
for experimental design for this approach, which may identify the target molecules of
such glycosyltransferases and related genes.
The aim of this book is to provide comprehensive coverage of all glycosyltrans
ferase genes and their related genes known at present. The nearly 100 chapters are
designed to summarize the present knowledge of these enzymes. The presentations
are brief and concise and are presented in a format that we hope will make compre
hension of the data relatively easy for readers.
More than fifty experts who have worked on their "pet" enzymes that were largely
purified and/or cloned by their group have contributed chapters on individual glyco
syltransferase genes and their related genes. We express our sincere thanks to all of
them for their enormous effort and detailed work. We are particularly grateful for the
assistance of the staff at Springer-Verlag Tokyo for their patience during the prepa
ration of the original draft of this book and its editing.
This publication was supported in part by the Naito Foundation, a Grant-in-Aid for
Publication of Scientific Research Results No. 135313 from the Japan Society for the
Promotion of Science, and a Grant-in-Aid for Scientific Research on Priority Area No.
10178105 from the Ministry of Education, Science, Sports and Culture of Japan.
July 2001
Naoyuki Taniguchi
Koichi Honke
Minoru Fukuda
EDITORS
Co-editors
Henrik Clausen (University of Copenhagen, Copenhagen, Denmark)
James W. Dennis (Mount Sinai Hospital, Toronto, Canada)
Kiyoshi Furukawa (Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan)
Koichi Furukawa (Nagoya University, Nagoya, Japan)
Gerald W. Hart (Johns Hopkins University, Baltimore, USA)
Yoshio Hirabayashi (Riken, Wako, Japan)
Reiji Kannagi (Aichi Cancer Center, Nagoya, Japan)
Masao Kawakita (Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan)
Toshisuke Kawasaki (Kyoto University, Kyoto, Japan)
Koji Kimata (Aichi Medical University, Nagoya, Japan)
Taroh Kinoshita (Osaka University, Osaka, Japan)
Ulf Lindahl (Uppsala University, Uppsala, Sweden)
Takashi Muramatsu (Nagoya University, Nagoya, Japan)
Hisashi Narimatsu (National Institute of Advanced Industrial Science and
Technology, Tsukuba, Japan)
Masaki Saito (National Cancer Center Research Institute, Tokyo, Japan)
Harry Schachter (The Hospital for Sick Children, Toronto, Canada)
Joel H. Shaper (Johns Hopkins University, Baltimore, USA)
Pamela Stanley (Albert Einstein College of Medicine, New York, USA)
Kazuyuki Sugahara (Kobe Pharmaceutical University, Kobe, Japan)
Akemi Suzuki (Riken, Wako, Japan)
Lawrence A. Tabak (University of Rochester, Rochester, USA)
Shuichi Tsuji (Ochanomizu University, Tokyo, Japan)
Dirk H. Van den Eijnden (Vrije Universiteit, Amsterdam, The Netherlands)
Katsuko Yamashita (Sasaki Institute, Tokyo, Japan)
Masaki Yanagishita (Tokyo Medical and Dental University, Tokyo, Japan)
VII
Contents
Preface ......................................................... V
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. XVII
Glucosyltransferase
1. GlcCer Synthase (UDP-Glucose:Ceramide Glucosyltransferase, UGCG) 3
Y. HIRABAYASHI and S. ICHIKAWA
Galactosyltransferases
2. ~4-Galactosyltransferase-I ...................................... 11
N.L. SHAPER and I.H. SHAPER
3. ~4-Galactosyltransferase-II, -III, -IV, -v, -VI, and -VII. . . . . . . . . . . .. . . . . 20
KIYOSHI FURUKAWA and H. CLAUSEN
4. 133-Galactosyltransferase-I, -II, and -III ............................ 27
T. HENNET and E.G. BERGER
5. ~3-Galactosyltransferase-IV (GMI Synthase) 33
KorCHI FURUKAWA
6. 133-Galactosyltransferase-V . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
H. NARIMATSU
7. a3-Galactosyltransferase........................................ 44
D.H. VAN DEN EIJNDEN and D.H. IOZIASSE
8. GalCer Synthase (Ceramide Galactosyltransferase, CGT) 51
w.
STOFFEL
N-Acetylg Iu cosa m in yltra n sferases
9. N-Acetylglucosaminyltransferase-I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
P. STANLEY
IX
X Contents
10. N-Acetylglucosaminyltransferase-II 70
H. SCHACHTER
11. N-Acetylglucosaminyltransferase-III .............................. 80
Y. IKEDA and N. TANIGUCHI
12. N-Acetylglucosaminyltransferase-IV .............................. 87
M.T. MINOWA, S. OGURI, A. YOSHIDA, and M. TAKEUCHI
13. N-Acetylglucosaminyltransferase-V ........... . . . . . . . . . . . . . . . . . . . . 94
J.w. DENNIS
14. N-Acetylglucosaminyltransferase-VI .............................. 102
K. HONKE and N. TANIGUCHI
15. ~3-N-Acetylglucosaminyltransferase (Fringe) 107
R.S. HALTIWANGER
16. ~3-N-Acetylglucosaminyltransferase (iGnT) 114
M. FUKUDA
17. ~6-N -Acetylglucosaminyltransferase (I GnT ) 125
M. FUKUDA
18. Core 2 ~6-N-Acetylglucosaminyltransferase-I and -III ................ 133
M. FUKUDA, T. SCHWIENTEK, and H. CLAUSEN
19. Core 2 ~6-N-Acetylglucosaminyltransferase-II 143
M. FUKUDA and J.-c. YEH
20. a4-N-Acetylglucosaminyltransferase .............................. 151
J. NAKAYAMA
21. O-GlcNAc Transferase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 158
S.P.N. IYER and G.W. HART
N-Acetylgalactosaminyltransferases
22. Polypeptide N-Acetylgalactosaminyltransferases . . . . . . . . . . . . . . . . . . . .. 167
F.K. HAGEN, K.G. TEN HAGEN, and L.A. TABAK
23. ~4-N-Acetylgalactosaminyltransferase . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 174
KorCHI FURUKAWA
24. Histoblood Group A and B Transferases, Their Gene Structures,
and Common 0 Group Gene Structures ........................... 180
S. HAKOMORI
25. Histoblood Group A Variants, 0 Variants, and Their Alleles 189
S. HAKOMORI
26. Forssman Glycolipid Synthase 197
K. HONKE
Contents XI
Fucosyltra nsferases
27. a2-Fucosyltransferases (FUn, FUT2, and Secl) 205
R. ORIOL and R. MOLLICONE
28. a3/4-Fucosyltransferase (FUT3, Lewis enzyme) 218
H. NARIMATSU
29. a3-Fucosyltransferase-IV (FUT4) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 226
H. NARIMATSU
30. a3-Fucosyltransferase-V (FUT5) 232
R. KANNAGI
31. a3-Fucosyltransferase-VI (FUT6) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 237
R. KANNAGI
32. a3-Fucosyltransferase-VII (FUT7) 246
H. NARIMATSU
33. a3-Fucosyltransferase-IX (FUT9) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 252
H. NARIMATSU
34. a6-Fucosyltransferase (FUT8) ................................... 259
E. MIYOSHI and N. TANIGUCHI
Sialyltransferases
35. ST3Gal-I 267
M. FUKUDA and J.D. MARTH
36. ST3Gal-II (SAT-IV) ............................................ 274
T. HAMAMOTO and S. TsuJI
37. ST3Gal-III 279
S. KITAZUME-KAWAGUCHI and S. TsuJI
38. ST3Gal-IV 284
S. KITAZUME-KAWAGUCHI and S. TSUJI
39. ST3Gal-V (GM3 Synthase, SAT-I) ................................. 289
M. SAITO and A. ISHII
40. ST6Gal-I 295
T. HAMAMOTO and S. TsuJI
41. ST6GalNAc-I ................................................. 301
N. KUROSAWA and S. TSUJI
42. ST6GalNAc-II ................................................ 306
N. KUROSAWA and S. TSUJI
43. ST6GalNAc-III (STY) .......................................... 311
S. TAKASHIMA and S. TsuJI
XII Contents
44. ST6GalNAc-IV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 317
S. TAKASHIMA and S. TSUJI
45. ST8Sia-I (GD3 Synthase, SAT-II) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 323
Y. SANAI
46. ST8Sia-II (STX) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 329
N. KOJIMA and S. TsuJI
47. ST8Sia-III 335
Y. YOSHIDA and S. TSUJI
48. ST8Sia-IV (PST-I) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 340
J. NAKAYAMA, K. ANGATA, M. SUZUKI, and M. FUKUDA
49. ST8Sia-V (SAT-V/SAT-III) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 347
M. KaNa and S. TsuJI
50. CMP-NeuAc Hydroxylase 352
A. SUZUKI
Glucuronyltransferases
51. HNK-l Glucuronyltransferase ................................... 359
S. OKA and T. KAWASAKI
52. GAG Glucuronyltransferase-I .................................... 368
H. KITAGAWA and K. SUGAHARA
53. UDP-Glucose Dehydrogenase 375
A.P. SPICER
GAG Synthesis
54. a4-N-Acetylhexosaminyltransferase (EXTL2) ....................... 385
H. KITAGAWA and K. SUGAHARA
55. Hyaluronan Synthase-I, -2, and -3 ................................ 392
K. KIMATA
56. Heparan Sulfate GlcA/GlcNAc Transferase . . . . . . . . . . . . . . . . . . . . . . . . .. 397
M. KUSCHE-GULLBERG and U. LINDAHL
57. D-Glucuronyl C5-Epimerase in HeparinlHeparan Sulfate Biosynthesis 403
J.-P. LI and U. LINDAHL
Sulfotransferases
58. Chondroitin 6-Sulfotransferase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 413
O. HABUCHI
59. Keratan Sulfate Gal-6-Sulfotransferase . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 418
M. FUKUTA and O. HABUCHI
