O-linked fucose and other post-translational modifications unique to EGF modules.
Three types of unusual post-translational modification have been found within conserved amino acid sequences in epidermal growth factor homology regions (EGF modules) of some multidomain proteins. beta-Hydroxyaspartate and beta-hydroxyasparagine are found within -Cys-Xxx-Asp/Asn-Xxx-Xxx-Xxx-Xxx-Tyr/Phe-Xxx-Cys-Xxx-Cys- sequences. (Xyl alpha 1-->3)Xyl alpha 1-->3Glc beta 1-->O-Ser glycans at conserved sites within -Cys-Xxx-Ser-Xxx-Pro-Cys- sequences have been reported in several proteins. Fuc alpha 1-->O-Thr/Ser modifications have been found at conserved sites within -Cys-Xxx-Xxx-Gly-Gly-Thr/Ser-Cys- sequences. More recently, it has been discovered that the Ser residue corresponding to the potential O-fucosylation site in human factor IX carries the novel tetrasaccharide NeuAc alpha 2-->6Gal beta 1-->4GlcNAc beta 1-->3Fuc alpha 1-->O-Ser; this tetrasaccharide can be considered to be an extension of the Fuc alpha 1-->O moiety. The consensus sequences for these post-translational modifications are in close proximity to each other; e.g. human factor IX has all three unusual modifications within a 12 amino acid linear sequence. In proteins with multiple EGF modules, the O-glycosidic modifications have been found only within the N-terminal EGF module; beta-hydroxyaspartate/asparagine residues are not restricted in the same fashion. Little is known yet about the functions of, or possible relationships between, any of these modifications.
Harris
R J
RJ
Department of Medicinal and Analytical Chemistry, Genentech, Inc., South San Francisco, CA 94080.
Spellman
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis; D002240:Carbohydrate Sequence; D017124:Conserved Sequence; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D005643:Fucose / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid
D001779:Blood Coagulation Factors; D006023:Glycoproteins; D005643:Fucose; D004815:Epidermal Growth Factor