[Gla-containing proteins]
1Department of Hygienic Sciences, Kobe Pharmaceutical University, Japan.
Abstract:
To date, 16 Gla-containing proteins have been discovered in humans, 7 and 9 of which are involved or not-involved in the blood coagulation cascade, respectively. They have a common feature that the carbon at the γ-position of glutamic acid in the specific amino acid sequence of the protein molecule is carboxylated. γ-Glutamyl carboxylase catalyzes this reaction in the presence of vitamin K as a cofactor. Similar to phosphorylation and glycosylation, γ-carboxylation of the glutamic acid has been thought to be one of the post-translational modification for the activation of proteins. However, undercarboxylated, but not highly carboxylated osteocalcin has been found to exhibit regulatory activities of glucose metabolism and insulin sensitivity in mice, suggesting that there would be more comprehensive mechanisms in the regulation of protein functions by the carboxylation of glutamic acid and the decarboxylation of γ-glutamic acid.
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