title: The propeptide of rat bone gamma-carboxyglutamic acid protein shares homology with other vitamin K-dependent protein precursors.
abstract: The molecular cloning of bone gamma-carboxyglutamic acid (Gla) protein (BGP; osteocalcin) was accomplished by constructing a phage lambda gt11 cDNA library from the rat osteosarcoma cell line ROS 17/2 and screening this library with antibodies raised against BGP from rat bone. By sequencing several cloned cDNAs, we have established a 489-base-pair sequence that predicts a mature BGP of 50 amino acid residues with an NH2-terminal extension of 49 residues. The leader peptide consists of a hydrophobic signal peptide followed by a basic propeptide of 26 or 27 residues that is cleaved after an Arg-Arg dipeptide prior to secretion from the cell. Mature rat BGP is extremely homologous to BGPs from other species except for its COOH-terminal sequence. A stretch of 9 residues proximal to the NH2 terminus of secreted BGP is strikingly similar to the corresponding regions in known propeptides of the gamma-carboxyglutamic acid-containing blood coagulation factors. We suggest that this common structural feature may be involved in the posttranslational targeting of these polypeptides for vitamin K-dependent gamma-carboxylation.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000276:immunology; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D015675:Osteocalcin; D011498:Protein Precursors; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014812:Vitamin K / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D015675:Osteocalcin; D014812:Vitamin K; D004247:DNA