beta-Hydroxyasparagine in domains homologous to the epidermal growth factor precursor in vitamin K-dependent protein S.
Vitamin K-dependent protein S is involved in the regulation of blood coagulation. It is a 75-kDa single chain protein with an NH2-terminal gamma-carboxyglutamic acid-containing domain followed by a thrombin-sensitive region and four domains arranged in tandem, each of which is homologous to the epidermal growth factor (EGF) precursor. The NH2-terminal EGF-like domain contains beta-hydroxyaspartic acid, which has been identified in vitamin K-dependent proteins. The following EGF-like repeat has a very pronounced sequence homology (10 consecutive residues identical) to one of the EGF-like units in the EGF precursor. We now show that, in protein S, this EGF-like repeat has one beta-hydroxyasparagine residue formed by hydroxylation of asparagine. The two COOH-terminal EGF-like repeats also contain beta-hydroxyasparagine, an amino acid not previously found in proteins. Sequence comparisons have enabled us to identify a consensus sequence that seems to be required by the hydroxylase(s).
D000595:Amino Acid Sequence; D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives* / Q000032:analysis; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis; D004815:Epidermal Growth Factor / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006900:Hydroxylation; D010446:Peptide Fragments / Q000032:analysis; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics; D017293:Protein S; D012689:Sequence Homology, Nucleic Acid
D006023:Glycoproteins; D010446:Peptide Fragments; D011498:Protein Precursors; D017293:Protein S; C042652:epidermal growth factor precursor; C050931:3-hydroxyasparagine; D004815:Epidermal Growth Factor; D001216:Asparagine; D004247:DNA