O-linked fucose and other post-translational modifications unique to EGF modules

Glycobiology. 1993 Jun;3(3):219-24. doi: 10.1093/glycob/3.3.219.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood Coagulation Factors / biosynthesis
  • Carbohydrate Sequence
  • Conserved Sequence
  • Epidermal Growth Factor / biosynthesis*
  • Fucose / metabolism*
  • Glycoproteins / biosynthesis*
  • Glycosylation
  • Humans
  • Molecular Sequence Data
  • Protein Processing, Post-Translational*
  • Sequence Homology, Amino Acid

Substances

  • Blood Coagulation Factors
  • Glycoproteins
  • Fucose
  • Epidermal Growth Factor