Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S.

Abstract

A 29-year-old female patient with heterozygous congenital protein S deficiency suffering from thrombotic disease had normal levels of both total and free protein S antigen (70% and 65%, respectively), but low cofactor activity (31%) for activated protein C, indicating that she had a variant of protein S, protein S Tokushima. Western blotting using the polyclonal anti-protein S antibody showed that approximately half of the patient's protein S appeared to be the variant with a higher molecular weight than normal protein S. The partially purified variant protein S bound neither to the monoclonal antibody recognizing calcium-dependent conformation of protein S nor to the antibody recognizing the thrombin-sensitive domain of protein S. Among the exons from II to XV of the patient's protein S gene encoding from the NH2-terminal end to the COOH-terminal end of protein S, only one missense mutation (A to G) was found in exon VI of the protein S alpha-gene, which results in amino acid substitution of Glu(GAG) for Lys-155(AAG) in the second epidermal growth factor-like domain of protein S. The recombinant protein S Tokushima expressed in BHK cells had a slightly higher molecular weight than the recombinant normal one, did not bind to the antibody specific for the thrombin-sensitive domain, and did not show the cofactor activity. These findings suggest that the protein S Tokushima molecule is structurally and functionally a variant of protein S, and that this variant protein S is the cause of severe thrombosis in this patient.

• Authors: T Hayashi, J Nishioka, T Shigekiyo, S Saito, K Suzuki
• Journal: Blood (Blood) Vol. 83 Issue 3 Pg. 683-90 (Feb 01 1994) ISSN: 0006-4971 [Print] United States
• PMID: 8298131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein S
• Recombinant Proteins
• Epidermal Growth Factor

Topics

• Adult
• Amino Acid Sequence
• Base Sequence
• Epidermal Growth Factor (chemistry)
• Exons
• Female
• Humans
• Introns
• Molecular Sequence Data
• Mutation
• Protein Conformation
• Protein S (chemistry, genetics)
• Protein S Deficiency
• Recombinant Proteins (chemistry)
• Thrombosis (genetics)