Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1)

Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1) is an enzyme that catalyzes the transfer of a sulfate group to the 2-position of iduronic acid or glucuronic acid residues within heparan sulfate, a critical step in the synthesis of sulfated glycosaminoglycan chains[1][5]. This post-synthetic modification of heparan sulfate strongly influences its biological activity, impacting cell-cell communication, growth factor signaling (such as FGF2 and EGFR), and organogenesis, particularly kidney development. Loss of HS2ST1 function in animal models leads to severe developmental abnormalities, including renal agenesis[1][4][5]. Dysregulation of HS2ST1 is implicated in cancer biology, notably breast cancer, where altered expression affects cell adhesion, migration, invasiveness, and cancer stem cell markers via changes to the MAPK, Notch, and Wnt signaling pathways[2][3]. While no approved drugs specifically target HS2ST1 as of now, its enzymatic activity and downstream effects make it of interest as a potential therapeutic target for diseases related to abnormal heparan sulfate modification, including cancer and developmental disorders.

Other names

HS2STKIAA04482-OST2OST2-O-sulfotransferaseHS 2-O-sulfotransferaseHeparan sulfate 2-sulfotransferaseNFSRAdJ604K5.2

Inhibitors or modulators of HS2ST1 would alter heparan sulfate structure, affecting binding and signaling of growth factors such as FGF2 and EGF - Interference with sulfation can impact cell signaling pathways related to growth, adhesion, and migration