Heparan Sulfate 6-O-Sulfotransferase 3/HS6ST3: Proteins and Enzymes

Heparan sulfate is a highly sulfated polysaccharide that can be found on the cell surface and extracellular matrix. It is usually covalently attached to a protein core as the glycan component of a proteoglycan. Heparan sulfate interacts with a variety of proteins, such as growth factors, protease inhibitors, cytokines, lipoprotein lipase and viral envelope proteins, therefore playing roles in cell growth, cell differentiation, cell motility, blood coagulation, lipid metabolism and viral infection. Heparan sulfate consists of repeating residues of uronic acid and N-acetylglucosamine. The uronic acid residues can be sulfated at the 2-O position by heparan sulfate 2-O-sulfotransferase. The N-acetylglucosamine residues can be sulfated at N-, 3-O, and 6-O positions by N-deacetylase/N-sulfotransferases, heparan sulfate 3-O- and 6-O-sulfotransferases, respectively. However, the reactions catalyzed by these sulfotransferases are normally incomplete on the whole chain of heparan sulfate. As a result, heparan sulfate displays enormous sequence diversity that allows it to interact with a wide spectrum of proteins differently. Three heparan sulfate 6-O-sulfotransferases are found both in human and mouse possibly with overlapping substrate specificity. HS6ST3 is ubiquitously expressed while HS6ST1 and HS6ST2 are expressed primarily in the liver and brain/spleen, respectively. Mouse HS6ST3 has 94% amino acid sequence identity with the human ortholog.