PROSITE documentation PDOC00927

Glypicans signature

Glypicans [1,2] are a family of heparan sulfate proteoglycans which are anchored to cell membranes by a glycosylphosphatidylinositol (GPI) linkage. Structurally, these proteins consist of three separate domains:

 a) A signal sequence;
 b) An  extracellular  domain of about 500 residues that contains 12 conserved
    cysteines probably involved in disulfide bonds and which also contains the
    sites of attachment of the heparan sulfate glycosaminoglycan side chains;
 c) A  C-terminal  hydrophobic  region  which  is post-translationally removed
    after formation of the GPI-anchor.

The proteins known to belong to this family are:

• Glypican 1 (GPC1).
• Glypican 2 (GPC2) or cerebroglycan.
• Glypican 3 (GPC3) or OCI-5. In man, defects in GPC3 are the cause of a X- linked genetic disease, Simpson-Galabi-Behmel syndrome (SGBS).
• Glypican 4 (GPC4) or K-glypican.
• Glypican 5 (GPC5).
• Glypican 6 (GPC6).
• Drosophila protein dally.

The signature pattern that we developed for glypicans is located in the central section of the extracellular domain and contains five of the conserved cysteines.