Glypican

The glypican family of heparan sulfate proteoglycans are anchored to the cell-surface via a covalent linkage to glycosylphosphatidylinositol (GPI). Six glypican family members have been identified in vertebrates, two in Drosophila and one in C. elegans.

Glypicans can modify cell signaling pathways and contribute to cellular proliferation and tissue growth. In Drosophila, the glypican dally assists diffusion of the BMP-family growth-promoting morphogen Decapentaplegic in the developing wing, while the developing haltere lacks dally and remains small. Extracellular localization of the other glypican in Drosophila, dally-like, is also required for the proper level of Hedgehog signaling in the developing wing.

In humans, glypican-1 is overexpressed in breast and brain cancers (gliomas), while glypican-3 is overexpressed in liver cancers.

Structure
All glypicans contain an N-terminal signal peptide and a hydrophobic domain in their C-terminal region, required for attachment of the GPI anchor. The amino acid sequences of the six vertebrate glypican family members vary from being 17% to 63% identical. The location of 14 cysteine amino acids is conserved between the glypicans, suggesting the existence of a highly similar three-dimensional structure. Heparan sulfate glycosaminoglycan chains are attached at the 50 amino acids at the C-terminal end of the protein, near the anchor and the cell membrane.