beta-Hydroxyasparagine in domains homologous to the epidermal growth factor precursor in vitamin K-dependent protein S

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Abstract

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).

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry

Keywords

  • Hydroxylation, *Glycoproteins/genetics, *Epidermal Growth Factor/genetics, DNA/analysis, Comparative Study, High Pressure Liquid, Chromatography, Cattle, Asparagine/*analogs & derivatives/analysis, Amino Acid Sequence, Animals, Peptide Fragments/analysis, Protein Conformation, *Protein Precursors/genetics, Protein S, Research Support, Non-U.S. Gov't, Sequence Homology, Nucleic Acid
Original languageEnglish
Pages (from-to)368-72
JournalProc Natl Acad Sci U S A
Volume84
Issue number2
Publication statusPublished - 1987
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

2