Fig. 6.

Schematic of the heparan sulfate biosynthesis. Heparan sulfate biosynthesis on serine residues of proteoglycans is illustrated according to (41). Enzymes involved in the individual steps are indicated. The tri-saccharide precursor generated by GlucAT1 activity can also give rise to chondroitin and dermatan sulfate glycosaminoglycans (not depicted). Heparan sulfate polymerization is catalyzed by successive addition of β1,4GlcA and α1,4GlcNAc by the EXT1/EXT2 heterodimer. SPPL3 substrates identified in the secretome analysis in HEK293 cells overexpressing SPPL3 (red boxes), in Sppl3-deficient MEF (green boxes), and in both (box filled with red-to-green gradient) are highlighted.