Primary structure of bovine matrix Gla protein, a new vitamin K-dependent bone protein.
The complete amino acid sequence of bovine bone matrix Gla protein (MGP) was determined by automatic sequence analysis of the intact protein and of peptides isolated from tryptic and BNPS-skatole digests. This 79-residue, vitamin K-dependent protein contains a single disulfide bond and 4.8 gamma-carboxyglutamate (Gla) residues, one each at positions 37, 41, 48, and 52, and 0.8 Gla and 0.2 Glu at position 2. There is sufficient sequence homology between MGP and bone Gla protein (BGP) to indicate that these two bovine bone proteins arose by gene duplication and subsequent divergent evolution. Although MGP has a very low solubility in water compared to BGP, there is no hydrophobic domain in MGP which could account for its insolubility, and the overall fraction of hydrophobic residues is 32% for MGP compared to 43% for BGP. MGP is the first vitamin K-dependent protein to be discovered which has several non-gamma-carboxylated residues to the NH2-terminal side of its Gla residues. The presence of NH2-terminal Glu residues between the putative targeting domain for the gamma-carboxylase in the MGP leader sequence and the mid-molecule Gla residues suggests that the gamma-carboxylase may have additional, as yet unrecognized, specificity requirements which determine the susceptibility of Glu residues for gamma-carboxylation.
D015055:1-Carboxyglutamic Acid / Q000032:analysis; D000595:Amino Acid Sequence; D000818:Animals; D001322:Autoanalysis; D002135:Calcium-Binding Proteins / Q000032:analysis*; D002268:Carboxypeptidases / Q000378:metabolism; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000032:analysis; D016326:Extracellular Matrix Proteins; D015675:Osteocalcin; D012862:Skatole / Q000031:analogs & derivatives; D012995:Solubility; D014357:Trypsin / Q000378:metabolism; D014812:Vitamin K / Q000378:metabolism*; D014867:Water; D000097568:Matrix Gla Protein
D015055:1-Carboxyglutamic Acid; D002135:Calcium-Binding Proteins; D002268:Carboxypeptidases; D004220:Disulfides; D016326:Extracellular Matrix Proteins; D015675:Osteocalcin; D012862:Skatole; D014357:Trypsin; D014812:Vitamin K; D014867:Water; D000097568:Matrix Gla Protein; C005904:BNPS-skatole; C022633:serine carboxypeptidase