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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lind, B. Articles by Thorsen, S. Search for Related Content PubMed PubMed Citation Articles by Lind, B. Articles by Thorsen, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Naturally occurring Arg(-1) to His mutation in human protein C leads to aberrant propeptide processing and secretion of dysfunctional protein C B Lind, AH Johnsen and S Thorsen Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. The dysfunctional protein C from a thrombophilic patient heterozygote for a G1388 to A converting the codon for Arg(-1) to His was purified from plasma and characterized. N-terminal amino acid sequence analysis of the light chain of the protein C demonstrated that the dysfunctional protein C is elongated with one amino acid, namely the mutated His. This finding is compatible with disruption by the mutated His of the original basic propeptidase recognition sequence (Arg(-5)-Ile-Arg-Lys- Arg(-1)), resulting in a shift of the cleavage site to a new position, Lys(-2)-His(-1), which follows an alternative basic amino acid propeptidase recognition sequence (Arg(-5)-Ile-Arg-Lys(-2)). Because the mutation affects the propeptide that directs the gamma- carboxylation converting Glu to Gla residues in the Gla domain, it was investigated whether the mutation impaired this reaction. Gla fragment obtained by cleavage of the dysfunctional protein C light chain with endoproteinase Asp-N was isolated by reverse-phase high-performance liquid chromatography, methylated, and subjected to N-terminal sequence analysis. The methylation step enabled the positive identification of Gla residues as well as the determination of the relative amount of Gla and Glu residues at each of the nine gamma-carboxylation sites of the Gla domain. The analysis showed that all nine potential gamma- carboxylation sites of the dysfunctional protein C were normally carboxylated. This result is compatible with the notion that position - 1 is not a part of the recognition element for the gamma-carboxylase. In conclusion, evidence is provided showing that the mutation leads to aberrant propeptide processing and secretion of dysfunctional normally carboxylated protein C extended with the mutated His. Volume 89, Issue 8, pp. 2807-2816, 04/15/1997 Copyright © 1997 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. S. Torekov, L. H. Larsen, C. Glumer, K. Borch-Johnsen, T. Jorgensen, J. J. Holst, O. D. Madsen, T. Hansen, and O. Pedersen Evidence of an Association Between the Arg72 Allele of the Peptide YY and Increased Risk of Type 2 Diabetes Diabetes, July 1, 2005; 54(7): 2261 - 2265. [Abstract] [Full Text] [PDF]

	Copyright © 1997 by American Society of Hematology         Online ISSN: 1528-0020