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 posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid, an amino acid critical to the function of the vitamin K-dependent blood coagulation proteins. Given the functional similarity of mammalian vitamin K-dependent 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. Furthermore, we examined the diversity of animal species that maintain vitamin K-dependent 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), hagfish (Myxine glutinosa), horseshoe crab (Limulus polyphemus), and cone snail (Conus textile) to compare these structures to the known bovine, human, rat, and mouse cDNA sequences. Comparison of the predicted amino acid sequences identified a nearly perfectly conserved 38-amino acid residue region in all of these putative carboxylases. In addition, this amino acid motif is also present in the Drosophila genome and identified a Drosophila homolog of the gamma-carboxylase. Assay of hagfish liver demonstrated vitamin K-dependent carboxylase activity in this hemichordate. These results demonstrate the broad distribution of the vitamin K-dependent carboxylase gene, including a highly conserved motif that is likely critical for enzyme function. The vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid appears to be a highly conserved function in the animal kingdom.
Begley
G S
GS
Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA.
Furie
B C
BC
Czerwiec
E
E
Taylor
K L
KL
Furie
G L
GL
Bronstein
L
L
Stenflo
J
J
Furie
B
B
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019735:Carbon-Carbon Ligases / Q000737:chemistry* / Q000235:genetics*; D002645:Chickens; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005399:Fishes / Q000235:genetics; D006196:Hagfishes / Q000235:genetics; D006801:Humans; D007448:Invertebrates / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014812:Vitamin K / Q000378:metabolism*; D014907:Whales / Q000235:genetics
D014812:Vitamin K; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase