Sulf2

Sulf2, also known as SULF2, is a human enzyme that belongs to the sulfatase family. It functions as an extracellular heparan sulfate 6-O-endosulfatase, removing 6-O-sulfate groups from heparan sulfate (HS) chains on proteoglycans located on the cell surface and in the extracellular matrix. In some contexts, the enzyme can be secreted or associated with the cell surface.

By desulfating HS, SULF2 modulates the binding affinity of HS for a wide range of heparin-binding ligands, including fibroblast growth factors (FGF), vascular endothelial growth factor (VEGF), Wnt proteins, and Hedgehog ligands, as well as their receptors. This remodeling of HS sulfation patterns can either enhance or suppress signaling through these pathways, depending on the cellular context, ligand availability, and receptor expression. Through these effects, SULF2 influences processes such as cell proliferation, differentiation, angiogenesis, and tissue morphogenesis.

Biochemical and regulatory properties: SULF2 is a catalytic, formylglycine-dependent sulfatase that requires post-translational activation for activity. Like other members of the extracellular sulfatase family, it is glycosylated and secreted, and its activity is modulated by the extracellular environment.

Biological and clinical significance: SULF2 participates in development and tissue homeostasis, with expression patterns that are tissue- and context-dependent. Altered SULF2 expression has been observed in various cancers, where it can play tumor-promoting or tumor-suppressing roles depending on the tumor type and microenvironment. Because it fine-tunes multiple signaling pathways via HS desulfation, SULF2 is of interest as a potential biomarker and therapeutic target.