Heparan sulfate-glucosamine 3-O-sulfotransferase 6 (HS3ST6)

Heparan sulfate-glucosamine 3-O-sulfotransferase 6 (HS3ST6) is an enzyme resident primarily in the Golgi membrane that catalyzes the transfer of sulfo groups to the 3-O position of glucosamine units in heparan sulfate chains using PAPS as the sulfo donor. This modification is rare but functionally critical, as 3-O-sulfated HS motifs mediate protein interactions involved in cell signaling, blood coagulation, and viral pathogenesis—particularly as receptors for Herpes simplex virus-1. The expression and function of HS3ST6 are implicated in hereditary angioedema, cancer, and other diseases. The HS3ST family includes seven human isoforms, each with discrete substrate specificity and biological roles. HS3ST6 does not participate in anticoagulant heparan sulfate generation, distinguishing it from family members like HS3ST1 and HS3ST5. Modulating HS3ST6 or related enzymes remains an area of active research for novel therapeutic strategies.

Other names

HS3ST63-OST-6h3-OST-6Heparan sulfate glucosamine 3-O-sulfotransferase 6Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 63OST6HAE8Heparan sulfate sulphate D-glucosaminyl 3-O-sulfotransferase-3B-like

Inhibition or modification of HS3ST6 may reduce 3-O-sulfation, altering heparan sulfate-protein interactions (e.g., preventing HSV-1 entry, modulating anticoagulant activity)