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Gene Review

CHST2  -  carbohydrate (N-acetylglucosamine-6-O)...

Homo sapiens

Synonyms: C6ST, Carbohydrate sulfotransferase 2, GN6ST, GST-2, GST2, ...
 
 
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Disease relevance of CHST2

  • CONCLUSIONS: The decrease in GlcNAc6ST activity in the cornea with MCD may result in the occurrence of low- or nonsulfated KS and thereby cause corneal opacity [1].
  • In contrast, GlcNAc6ST activity in the extracts from MCD-affected corneas, which was measured by using oligo A as an acceptor, was much lower than in those in corneas with keratoconus and in normal control corneas [1].
  • The amount of glutathione S-transferase-2 (GST-2) protein and enzyme activity in a mutant strain (strain GG) of the yellow fever mosquito (Aedes aegypti) is approximately 25-fold higher than in the wild-type (++) strain [2].
  • In adult mice, brain injury apparently upregulates mRNA expression of N-acetylglucosamine 6-O-sulfotransferase-1 as well as 5D4-reactive KS in the wounded area [3].
  • Human GlcNAc6ST-1 was expressed as a fusion protein with protein A in an insect cell line (Tn 5 cells) using the baculovirus system [4].
 

High impact information on CHST2

  • Recently, three related sulfotransferases (keratan sulfate galactose-6-sulfotransferase [KSGal6ST], high endothelial cell N-acetylglucosamine-6-sulfotransferase [GlcNAc6ST], and human GlcNAc6ST) were cloned, which can generate Gal-6-sulfate and GlcNAc-6-sulfate in GlyCAM-1 [5].
  • To ascertain the importance of the carbohydrate chain sulfation step in KS functionality, we generated a strain of mice with a targeted gene deletion in Chst5, which encodes an N-acetylglucosamine-6-O-sulfotransferase that is integral to the sulfation of KS chains [6].
  • We applied this strategy to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 and GlcNAc6ST-2, which collaborate in the sulfation of L-selectin ligands [7].
  • Collectively, these results indicate that the stem region of GlcNAc6ST-1 influences substrate specificity, independent of its role in dimerization or Golgi retention [8].
  • Two members of this family, GlcNAc6ST-1 and -2, collaborate in the biosynthesis of ligands for the leukocyte adhesion molecule L-selectin [8].
 

Chemical compound and disease context of CHST2

 

Biological context of CHST2

 

Anatomical context of CHST2

  • These results suggest that CHST1 and CHST2 contribute to the generation of optimal L-selectin ligands in vascular endothelial cells at sites of inflammation [10].
  • CHST1 and CHST2 sulfotransferase expression by vascular endothelial cells regulates shear-resistant leukocyte rolling via L-selectin [10].
  • A human umbilical vein endothelial cell line, EA.hy926, displayed functional L-selectin ligands that correlated with CHST1 and CHST2 expression in the absence of CHST4 expression [10].
  • We have isolated three novel organic anion transporter cDNAs designated rat GST-1 (gonad-specific transporter), rat GST-2, and human GST, expressed at high levels in the testis [14].
  • In houseflies, there were 60 pmol of GST-2/fly, 80-90% being found in the thorax, about 10% in the head and the remainder in the abdomen [15].
 

Associations of CHST2 with chemical compounds

 

Regulatory relationships of CHST2

 

Other interactions of CHST2

  • Both GlcNAc6ST-1 and GlcNAc6ST-2 efficiently utilized the following oligosaccharide structures as acceptors: GlcNAcbeta1-6[Galbeta1-3]GalNAc-pNP (core 2), GlcNAcbeta1-6ManOMe, and GlcNAcbeta1-2Man [16].
  • CHST1 and CHST2 sulfotransferases expressed by human vascular endothelial cells: cDNA cloning, expression, and chromosomal localization [11].
  • Indeed, cells doubly transfected with GlcNAc6ST-1 and fucosyltransferase VII cDNAs supported the rolling of L-selectin-expressing cells [16].
  • The data indicate that GST-6 is composed of two dissimilar subunits that do not cross-react with antiserum directed against GST-1, GST-2 or GST-3 [20].
  • This demonstrates the induction of GlcNAc6STs in human monocytes in response to TNF-alpha and implicates GlcNAc6ST-1 in the generation of the 6-sulfo LacNAc/Lewis x epitope on CD44 [19].
 

Analytical, diagnostic and therapeutic context of CHST2

References

  1. Decreased GlcNAc 6-O-sulfotransferase activity in the cornea with macular corneal dystrophy. Hasegawa, N., Torii, T., Kato, T., Miyajima, H., Furuhata, A., Nakayasu, K., Kanai, A., Habuchi, O. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  2. Genetic and molecular evidence for a trans-acting regulatory locus controlling glutathione S-transferase-2 expression in Aedes aegypti. Grant, D.F., Hammock, B.D. Mol. Gen. Genet. (1992) [Pubmed]
  3. Brain keratan sulfate and glial scar formation. Zhang, H., Uchimura, K., Kadomatsu, K. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  4. N-acetylglucosamine-6-O-sulfotransferase-1: production in the baculovirus system and its applications to the synthesis of a sulfated oligosaccharide and to the modification of oligosaccharides in fibrinogen. El-Fasakhany, F.M., Ichihara-Tanaka, K., Uchimura, K., Muramatsu, T. J. Biochem. (2003) [Pubmed]
  5. Sulfation of a high endothelial venule-expressed ligand for L-selectin. Effects on tethering and rolling of lymphocytes. Tangemann, K., Bistrup, A., Hemmerich, S., Rosen, S.D. J. Exp. Med. (1999) [Pubmed]
  6. Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6-O-sulfotransferase. Hayashida, Y., Akama, T.O., Beecher, N., Lewis, P., Young, R.D., Meek, K.M., Kerr, B., Hughes, C.E., Caterson, B., Tanigami, A., Nakayama, J., Fukada, M.N., Tano, Y., Nishida, K., Quantock, A.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. A small-molecule switch for Golgi sulfotransferases. de Graffenried, C.L., Laughlin, S.T., Kohler, J.J., Bertozzi, C.R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. The stem region of the sulfotransferase GlcNAc6ST-1 is a determinant of substrate specificity. de Graffenried, C.L., Bertozzi, C.R. J. Biol. Chem. (2004) [Pubmed]
  9. Beta-carbonyl substituted glutathione conjugates as inhibitors Of O. volvulus GST2. Brophy, P.M., Campbell, A.M., van Eldik, A.J., Teesdale-Spittle, P.H., Liebau, E., Wang, M.F. Bioorg. Med. Chem. Lett. (2000) [Pubmed]
  10. CHST1 and CHST2 sulfotransferase expression by vascular endothelial cells regulates shear-resistant leukocyte rolling via L-selectin. Li, X., Tu, L., Murphy, P.G., Kadono, T., Steeber, D.A., Tedder, T.F. J. Leukoc. Biol. (2001) [Pubmed]
  11. CHST1 and CHST2 sulfotransferases expressed by human vascular endothelial cells: cDNA cloning, expression, and chromosomal localization. Li, X., Tedder, T.F. Genomics (1999) [Pubmed]
  12. Golgi localization of carbohydrate sulfotransferases is a determinant of L-selectin ligand biosynthesis. de Graffenried, C.L., Bertozzi, C.R. J. Biol. Chem. (2003) [Pubmed]
  13. Molecular cloning and characterization of an N-acetylglucosamine-6-O-sulfotransferase. Uchimura, K., Muramatsu, H., Kadomatsu, K., Fan, Q.W., Kurosawa, N., Mitsuoka, C., Kannagi, R., Habuchi, O., Muramatsu, T. J. Biol. Chem. (1998) [Pubmed]
  14. Identification and characterization of novel rat and human gonad-specific organic anion transporters. Suzuki, T., Onogawa, T., Asano, N., Mizutamari, H., Mikkaichi, T., Tanemoto, M., Abe, M., Satoh, F., Unno, M., Nunoki, K., Suzuki, M., Hishinuma, T., Goto, J., Shimosegawa, T., Matsuno, S., Ito, S., Abe, T. Mol. Endocrinol. (2003) [Pubmed]
  15. Glutathione S-transferases in housefly (Musca domestica): location of GST-1 and GST-2 families. Franciosa, H., Bergé, J.B. Insect Biochem. Mol. Biol. (1995) [Pubmed]
  16. Specificities of N-acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression. Uchimura, K., El-Fasakhany, F.M., Hori, M., Hemmerich, S., Blink, S.E., Kansas, G.S., Kanamori, A., Kumamoto, K., Kannagi, R., Muramatsu, T. J. Biol. Chem. (2002) [Pubmed]
  17. Cloning and characterization of a mammalian N-acetylglucosamine-6-sulfotransferase that is highly restricted to intestinal tissue. Lee, J.K., Bhakta, S., Rosen, S.D., Hemmerich, S. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  18. Human N-acetylglucosamine-6-O-sulfotransferase involved in the biosynthesis of 6-sulfo sialyl Lewis X: molecular cloning, chromosomal mapping, and expression in various organs and tumor cells. Uchimura, K., Muramatsu, H., Kaname, T., Ogawa, H., Yamakawa, T., Fan, Q.W., Mitsuoka, C., Kannagi, R., Habuchi, O., Yokoyama, I., Yamamura, K., Ozaki, T., Nakagawara, A., Kadomatsu, K., Muramatsu, T. J. Biochem. (1998) [Pubmed]
  19. Expression of N-acetylglucosamine 6-O-sulfotransferases (GlcNAc6STs)-1 and -4 in human monocytes: GlcNAc6ST-1 is implicated in the generation of the 6-sulfo N-acetyllactosamine/Lewis x epitope on CD44 and is induced by TNF-alpha. Tjew, S.L., Brown, K.L., Kannagi, R., Johnson, P. Glycobiology (2005) [Pubmed]
  20. Electrophoretic and immunological analysis of human glutathione S-transferase isozymes. Suzuki, T., Coggan, M., Shaw, D.C., Board, P.G. Ann. Hum. Genet. (1987) [Pubmed]
  21. Characterization and mutagenesis of Gal/GlcNAc-6-O-sulfotransferases. Grunwell, J.R., Rath, V.L., Rasmussen, J., Cabrilo, Z., Bertozzi, C.R. Biochemistry (2002) [Pubmed]
  22. Glucose screening test results in first and early third trimester of pregnancy: is there any correlation? Bhattacharya, S.M. J. Obstet. Gynaecol. Res. (2002) [Pubmed]
 
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