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).

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

Keyword

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

Publication and Content Type

art (subject category)

ref (subject category)