Skip to main content
SpringerLink
Log in
Book cover

Handbook of Glycosyltransferases and Related Genes pp 1053–1065Cite as

Heparan Sulfate 2-O-Sulfotransferase (HS2ST)

  • Reference work entry
  • First Online:

  • 294 Accesses

Abstract

Backbone structure of heparan sulfate (HS) and heparin is composed of HexA-GlcNAc/GlcNSO3 repeating units, in which HexA is either d-GlcA or l-IdoA, linked to core proteins through a tetrasaccharide linkage sequence, GlcA-Gal-Gal-Xyl. Sulfate groups are present on the position 2 of the HexA, position 3 and 6 of the GlcNAc/GlcNSO3, and position 2 in the GlcNSO3. Heparan sulfate 2-O-sulfotransferase (HS2ST) transfers sulfate from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to position 2 of the IdoA and GlcA residue in HS and heparin.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   799.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Ashikari-Hada S, Habuchi H, Kariya Y, Itoh N, Reddi AH, Kimata K (2004) Characterization of growth factor-binding structures in heparin/heparan sulfate using an octasaccharide library. J Biol Chem 279:12346–12354

    Article  CAS  PubMed  Google Scholar 

  • Ashikari-Hada S, Habuchi H, Kariya Y, Kimata K (2005) Heparin regulates vascular endothelial growth factor165-dependent mitogenic activity, tube formation, and its receptor phosphorylation of human endothelial cells. Comparison of the effects of heparin and modified heparins. J Biol Chem 280:31508–31515

    Article  CAS  PubMed  Google Scholar 

  • Ashikari-Hada S, Habuchi H, Sugaya N, Kobayashi T, Kimata K (2009) Specific inhibition of FGF-2 signaling with 2-O-sulfated octasaccharides of heparan sulfate. Glycobiology 19:644–654

    Article  CAS  PubMed  Google Scholar 

  • Axelsson J, Xu D, Kang BN, Nussbacher JK, Handel TM, Ley K, Sriramarao P, Esko JD (2012) Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice. Blood 120:1742–1751

    Article  CAS  PubMed  Google Scholar 

  • Bai X, Esko JD (1996) An animal cell mutant defective in heparan sulfate hexuronic acid 2-O-sulfation. J Biol Chem 271:17711–17717

    Article  CAS  PubMed  Google Scholar 

  • Bai X, Bame KJ, Habuchi H, Kimata K, Esko JD (1997) Turnover of heparan sulfate depends on 2-O-sulfation of uronic acids. J Biol Chem 272:23172–23179

    Article  CAS  PubMed  Google Scholar 

  • Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M (1999) Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 68:729–777

    Article  CAS  PubMed  Google Scholar 

  • Bethea HN, Xu D, Liu J, Pedersen LC (2008) Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis. Proc Natl Acad Sci USA 105:18724–18729

    Article  CAS  PubMed  Google Scholar 

  • Bishop JR, Schuksz M, Esko JD (2007) Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446:1030–1037

    Article  CAS  PubMed  Google Scholar 

  • Bullock SL, Fletcher JM, Beddington RS, Wilson VA (1998) Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding heparan sulfate 2-sulfotransferase. Genes Dev 12:1894–1906

    Article  CAS  PubMed  Google Scholar 

  • Bülow HE, Hobert O (2004) Differential sulfations and epimerization define heparan sulfate specificity in nervous system development. Neuron 41:723–736

    Article  PubMed  Google Scholar 

  • Bülow HE, Hobert O (2006) The molecular diversity of glycosaminoglycans shapes animal development. Annu Rev Cell Dev Biol 22:375–407

    Article  PubMed  Google Scholar 

  • Conway CD, Howe KM, Nettleton NK, Price DJ, Mason JO, Pratt T (2011) Heparan sulfate sugar modifications mediate the functions of slits and other factors needed for mouse forebrain commissure development. J Neurosci 31:1955–1970

    Article  CAS  PubMed  Google Scholar 

  • DiGabriele AD, Lax I, Chen DI, Svahn CM, Jaye M, Schlessinger J, Hendrickson WA (1998) Structure of a heparin-linked biologically active dimer of fibroblast growth factor. Nature 393:812–817

    Article  CAS  PubMed  Google Scholar 

  • Fadel S, Eley A (2008) Differential glycosaminoglycan binding of Chlamydia trachomatis OmcB protein from serovars E and LGV. J Med Microbiol 57(Pt 9):1058–1061

    Article  CAS  PubMed  Google Scholar 

  • Faham S, Hileman RE, Fromm JR, Linhardt RJ, Rees DC (1996) Heparin structure and interactions with basic fibroblast growth factor. Science 271:1116–1120

    Article  CAS  PubMed  Google Scholar 

  • Guimond S, Maccarana M, Olwin BB, Lindahl U, Rapraeger AC (1993) Activating and inhibitory heparin sequences for FGF-2 (basic FGF). Distinct requirements for FGF-1, FGF-2, and FGF-4. J Biol Chem 268:23906–23914

    CAS  PubMed  Google Scholar 

  • Habuchi H, Suzuki S, Saito T, Tamura T, Harada T, Yoshida K, Kimata K (1992) Structure of a heparan sulphate oligosaccharide that binds to basic fibroblast growth factor. Biochem J 285:805–813

    CAS  PubMed  Google Scholar 

  • Habuchi H, Habuchi O, Kimata K (1995) Purification and characterization of heparan sulfate 6-sulfotransferase from the culture medium of Chinese hamster ovary cells. J Biol Chem 270:4172–4179

    Article  CAS  PubMed  Google Scholar 

  • Habuchi H, Kobayashi M, Kimata K (1998) Molecular characterization and expression of heparan-sulfate 6-sulfotransferase. Complete cDNA cloning in human and partial cloning in Chinese hamster ovary cells. J Biol Chem 273:9208–9213

    Article  CAS  PubMed  Google Scholar 

  • Habuchi H, Tanaka M, Habuchi O, Yoshida K, Suzuki H, Ban K, Kimata K (2000) The occurrence of three isoforms of heparan sulfate 6-O-sulfotransferase having different specificities for hexuronic acid adjacent to the targeted N-sulfoglucosamine. J Biol Chem 275:2859–2868

    Article  CAS  PubMed  Google Scholar 

  • Habuchi H, Habuchi O, Uchimura K, Kimata K, Muramatsu T (2006) Determination of substrate specificity of sulfotransferases and glycosyltransferases (proteoglycans). Methods Enzymol 416:225–243

    Article  CAS  PubMed  Google Scholar 

  • Irie F, Badie-Mahdavi H, Yamaguchi Y (2012) Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. Proc Natl Acad Sci USA 109:5052–5056

    Article  CAS  PubMed  Google Scholar 

  • Ishihara M, Takano R, Kanda T, Hayashi K, Hara S, Kikuchi H, Yoshida K (1995) Importance of 6-O-sulfate groups of glucosamine residues in heparin for activation of FGF-1 and FGF-2. J Biochem 118:1255–1260

    CAS  PubMed  Google Scholar 

  • Jastrebova N, Vanwildemeersch M, Rapraeger AC, Giménez-Gallego G, Lindahl U, Spillmann D (2006) Heparan sulfate-related oligosaccharides in ternary complex formation with fibroblast growth factors 1 and 2 and their receptors. J Biol Chem 281:26884–26892

    Article  CAS  PubMed  Google Scholar 

  • Jones KS, Lambert S, Bouttier M, Bénit L, Ruscetti FW, Hermine O, Pique C (2011) Molecular aspects of HTLV-1 entry: functional domains of the HTLV-1 surface subunit (SU) and their relationships to the entry receptors. Viruses 3:794–810

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kakuta Y, Pedersen LG, Carter CW, Negishi M, Pedersen LC (1997) Crystal structure of estrogen sulphotransferase. Nat Struct Biol 4:904–908

    Article  CAS  PubMed  Google Scholar 

  • Kamimura K, Koyama T, Habuchi H, Ueda R, Masu M, Kimata K, Nakato H (2006) Specific and flexible roles of heparan sulfate modifications in Drosophila FGF signaling. J Cell Biol 174:773–778

    Article  CAS  PubMed  Google Scholar 

  • Kan M, Wang F, Xu J, Crabb JW, Hou J, McKeehan WL (1993) An essential heparin-binding domain in the fibroblast growth factor receptor kinase. Science 259:1918–1921

    Article  CAS  PubMed  Google Scholar 

  • Kimata K, Habuchi O, Habuchi H, Watanabe H (2007) Knockout mice and proteoglycans in comprihensive glycoscience, vol 3. Elsevier, pp 119–159, Chapter 4.10

    Google Scholar 

  • Kinnunen T, Huang Z, Townsend J, Gatdula MM, Brown JR, Esko JD, Turnbull JE (2005) Heparan 2-O-sulfotransferase, hst-2, is essential for normal cell migration in Caenorhabditis elegans. Proc Natl Acad Sci USA 102:1507–1512

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi M, Habuchi H, Habuchi O, Saito M, Kimata K (1996) Purification and characterization of heparan sulfate 2-sulfotransferase from cultured Chinese hamster ovary cells. J Biol Chem 271:7645–7653

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi M, Habuchi H, Yoneda M, Habuchi O, Kimata K (1997) Molecular cloning and expression of Chinese hamster ovary cell heparan-sulfate 2-sulfotransferase. J Biol Chem 272:13980–13985

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi T, Habuchi H, Tamura K, Ide H, Kimata K (2007) Essential role of heparan sulfate 2-O-sulfotransferase in chick limb bud patterning and development. J Biol Chem 282:19589–19597

    Article  CAS  PubMed  Google Scholar 

  • Kolset SO, Pejler G (2011) Serglycin: a structural and functional chameleon with wide impact on immune cells. J Immunol 187:4927–4933

    Article  CAS  PubMed  Google Scholar 

  • Lindahl B, Eriksson L, Lindahl U (1995) Structure of heparan sulphate from human brain, with special regard to Alzheimer’s disease. Biochem J 306:177–184

    CAS  PubMed  Google Scholar 

  • MacArthur JM, Bishop JR, Stanford KI, Wang L, Bensadoun A, Witztum JL, Esko JD (2007) Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members. J Clin Invest 117:153–164

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maccarana M, Casu B, Lindahl U (1993) Minimal sequence in heparin/heparan sulfate required for binding of basic fibroblast growth factor. J Biol Chem 268:23898–23905

    CAS  PubMed  Google Scholar 

  • McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP, Tufaro F (1998) The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate. Nat Genet 19:158–161

    Article  CAS  PubMed  Google Scholar 

  • Melo FR, Grujic M, Spirkoski J, Calounova G, Pejler G (2012) Serglycin proteoglycan promotes apoptotic versus necrotic cell death in mast cells. J Biol Chem 287:18142–18152

    Article  CAS  PubMed  Google Scholar 

  • Merry CL, Bullock SL, Swan DC, Backen AC, Lyon M, Beddington RS, Wilson VA, Gallagher JT (2001) The molecular phenotype of heparan sulfate in the Hs2st−/− mutant mouse. J Biol Chem 276:35429–35434

    Article  CAS  PubMed  Google Scholar 

  • Merry CL, Wilson VA (2002) Role of heparan sulfate-2-O-sulfotransferase in the mouse. Biochim Biophys Acta 1573:319–327

    Article  CAS  PubMed  Google Scholar 

  • Moon AF, Edavettal SC, Krahn JM, Munoz EM, Negishi M, Linhardt RJ, Liu J, Pedersen LC (2004) Structural analysis of the sulfotransferase (3-O-sulfotransferase isoform 3) involved in the biosynthesis of an entry receptor for herpes simplex virus 1. J Biol Chem 279:45185–45193

    Article  CAS  PubMed  Google Scholar 

  • Nogami K, Suzuki H, Habuchi H, Ishiguro N, Iwata H, Kimata K (2004) Distinctive expression patterns of heparan sulfate O-sulfotransferases and regional differences in heparan sulfate structure in chick limb buds. J Biol Chem 279:8219–8229

    Article  CAS  PubMed  Google Scholar 

  • Perrimon N, Bernfield M (2000) Specificities of heparan sulphate proteoglycans in developmental processes. Nature 404:725–728

    Article  CAS  PubMed  Google Scholar 

  • Plotnikov AN, Schlessinger J, Hubbard SR, Mohammadi M (1999) Structural basis for FGF receptor dimerization and activation. Cell 98:641–650

    Article  CAS  PubMed  Google Scholar 

  • Pratt T, Conway CD, Tian NM, Price DJ, Mason JO (2006) Heparan sulphation patterns generated by specific heparan sulfotransferase enzymes direct distinct aspects of retinal axon guidance at the optic chiasm. J Neurosci 26:6911–6923

    Article  CAS  PubMed  Google Scholar 

  • Pye DA, Vives RR, Turnbull JE, Hyde P, Gallagher JT (1998) Heparan sulfate oligosaccharides require 6-O-sulfation for promotion of basic fibroblast growth factor mitogenic activity. J Biol Chem 273:22936–22942

    Article  CAS  PubMed  Google Scholar 

  • Qu X, Carbe C, Tao C, Powers A, Lawrence R, van Kuppevelt TH, Cardoso WV, Grobe K, Esko JD, Zhang X (2011) Lacrimal gland development and Fgf10-Fgfr2b signaling are controlled by 2-O- and 6-O-sulfated heparan sulfate. J Biol Chem 286:14435–14444

    Article  CAS  PubMed  Google Scholar 

  • Qu X, Pan Y, Carbe C, Powers A, Grobe K, Zhang X (2012) Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development. Development 139:2730–2739

    Article  CAS  PubMed  Google Scholar 

  • Rapraeger AC, Krufka A, Olwin BB (1991) Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation. Science 252:1705–1708

    Article  CAS  PubMed  Google Scholar 

  • Rong J, Habuchi H, Kimata K, Lindahl U, Kusche-Gullberg M (2001) Substrate specificity of the heparan sulfate hexuronic acid 2-O-sulfotransferase. Biochemistry 40:5548–5555

    Article  CAS  PubMed  Google Scholar 

  • Scholefield Z, Yates EA, Wayne G, Amour A, McDowell W, Turnbull JE (2003) Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer’s beta-secretase. J Cell Biol 163:97–107

    Article  CAS  PubMed  Google Scholar 

  • Selleck SB (2000) Proteoglycans and pattern formation: sugar biochemistry meets developmental genetics. Trends Genet 16:206–212

    Article  CAS  PubMed  Google Scholar 

  • Shively JE, Conrad HE (1976) Formation of anhydrosugars in the chemical depolymerization of heparin. Biochemistry 15:3932–3942

    Article  CAS  PubMed  Google Scholar 

  • Smeds E, Feta A, Kusche-Gullberg M (2010) Target selection of heparan sulfate hexuronic acid 2-O-sulfotransferase. Glycobiology 20:1274–1282

    Article  CAS  PubMed  Google Scholar 

  • Stanford KI, Wang L, Castagnola J, Song D, Bishop JR, Brown JR, Lawrence R, Bai X, Habuchi H, Tanaka M, Cardoso WV, Kimata K, Esko JD (2010) Heparan sulfate 2-O-sulfotransferase is required for triglyceride-rich lipoprotein clearance. J Biol Chem 285:286–294

    Article  CAS  PubMed  Google Scholar 

  • Stevens RL, Adachi R (2007) Protease-proteoglycan complexes of mouse and human mast cells and importance of their beta-tryptase-heparin complexes in inflammation and innate immunity. Immunol Rev 217:155–167

    Article  CAS  PubMed  Google Scholar 

  • Turnbull JE, Fernig DG, Ke Y, Wilkinson MC, Gallagher JT (1992) Identification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate. J Biol Chem 267:10337–10341

    CAS  PubMed  Google Scholar 

  • Wang L, Fuster M, Sriramarao P, Esko JD (2005) Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses. Nat Immunol 6:902–910

    Article  CAS  PubMed  Google Scholar 

  • Wlad H, Maccarana M, Eriksson I, Kjellén L, Lindahl U (1994) Biosynthesis of heparin. Different molecular forms of O-sulfotransferases. J Biol Chem 269:24538–24541

    CAS  PubMed  Google Scholar 

  • Yabushita H, Noguchi Y, Habuchi H, Ashikari S, Nakabe K, Fujita M, Noguchi M, Esko JD, Kimata K (2002) Effects of chemically modified heparin on Chlamydia trachomatis serovar L2 infection of eukaryotic cells in culture. Glycobiology 12:345–351

    Article  CAS  PubMed  Google Scholar 

  • Yayon A, Klagsbrun M, Esko JD, Leder P, Ornitz DM (1991) Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell 64:841–848

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Aichi Medical University, 480-1195, Nagakute, Aichi, Japan

    Dr. Hiroko Habuchi

Authors
  1. Dr. Hiroko Habuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroko Habuchi .

Editor information

Editors and Affiliations

  1. RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN, Wako, Saitama, Japan

    Naoyuki Taniguchi

  2. Department of Biochemistry, Kochi University, Medical School, Nankoku, Kochi, Japan

    Koichi Honke

  3. Sanford Burnham Medical Research Institute, La Jolla, California, USA

    Minoru Fukuda

  4. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan

    Hisashi Narimatsu

  5. RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN, Wako, Saitama, Japan

    Yoshiki Yamaguchi

  6. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

    Takashi Angata

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this entry

Cite this entry

Habuchi, H. (2014). Heparan Sulfate 2-O-Sulfotransferase (HS2ST). In: Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T. (eds) Handbook of Glycosyltransferases and Related Genes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54240-7_67

Download citation

Publish with us

Policies and ethics

Search

Navigation