A conserved motif within the vitamin K-dependent carboxylase gene is widely distributed across animal phyla

The vitamin K-dependent gamma -glutamyl carboxylase catalyzes the posttrans lational conversion of glutamic acid to gamma -carboxyglutamic acid, an ami no acid critical to the function of the vitamin K-dependent blood coagulati on proteins. Given the functional similarity of mammalian vitamin K-depende nt carboxylases and the vitamin K-dependent carboxylase from Conus textile, a marine invertebrate, we hypothesized that structurally conserved regions would identify sequences critical to this common functionality. Furthermor e, we examined the diversity of animal species that maintain vitamin K-depe ndent carboxylation to generate gamma -carboxyglutamic acid. We have cloned carboxylase homologs in full-length or partial form from the beluga whale (Delphinapterus leucas), toadfish (Opsanus tau), chicken (Gallus gallus), h agfish (Myxine glutinosa), horseshoe crab (Limulus polyphemus), and cone sn ail (Conus textile) to compare these structures to the known bovine, human, rat, and mouse cDNA sequences, Comparison of the predicted amino acid sequ ences identified a nearly perfectly conserved 38-amino acid residue region in all of these putative carboxylases. In addition, this amino acid motif i s also present in the Drosophila genome and identified a Drosophila homolog of the gamma -carboxylase, Assay of hagfish liver demonstrated vitamin K-d ependent carboxylase activity in this hemichordate. These results demonstra te the broad distribution of the vitamin K-dependent carboxylase gene, incl uding a highly conserved motif that is likely critical for enzyme function. The vitamin K-dependent biosynthesis of gamma -carboxyglutamic acid appear s to be a highly conserved function in the animal kingdom.