Glycosyltransferases Involved in O-fucose Glycan Synthesis

Abstract

Modification with O-fucose glycans is a rare type of post-translational modification found mainly on epidermal growth factor (EGF) domains. Although EGF domains are generally found on a number of secreted or cell surface glycoproteins, only a subset can be O-fucosylated. Founding members of those O-fucosylated proteins include urokinase in human urine and the coagulation/fibrinolytic proteins in blood plasma, such as blood clotting Factors VII, IX, and XII, and tissue plasminogen activator. Recently, a number of transmembrane proteins involved in the Notch signaling pathway have been identified as novel O-fucosylated glycoproteins. The extracellular domain of the Notch receptor is composed largely of a tandem array of EGF repeats (36 in Drosophila Notch and mammalian Notch1 and Notch2) and many of them are considered to be O-fucosylated. Similarly, Notch ligands (Delta, Serrate/Jagged) as well as Dlk-1/Pref-1, a negative regulator for Notch signaling, are also EGF repeat-containing proteins that are known to be O-fucosylated. By comparing the sequences surrounding the sites of O-fucose modification of those glycoproteins, the consensus amino acid sequence for O-fucosylation is proposed to be C2X3–5 S/TC3 (where C2 and C3 are the second and third conserved cysteine residue, respectively, X3–5 are any 3–5 amino acids, and S/T is the fucosylated amino acid) (Haltiwanger and Stanley 2002).