Amino acid sequence homology and the vitamin K-dependent proteins.

Examination of amino acid sequence data on bovine vitamin K-dependent clotting zymogens, using the Gibbs and McIntyre diagonal plot, leads to the conclusion that they are homologous and have evolved by a series of gene duplications. Plasminogen is also homologous but lacks the region containing glutamic acid (Glu) residues gamma-carboxylated in a vitamin K-dependent step. Both prothrombin and plasminogen show internal sequence homology resulting from partial gene duplication and quintuplication respectively; each internal homology loop in prothrombin shows significant homology with each of the five putative loops in plasminogen. Recently, Walz et al. (Proc. natn. Acad. Sci. USA 74: 1969-1972, 1977) have sequenced the non-thrombin region of human prothrombin (residues 1-273) and this has enabled identification of regions conserved in 90 million years of eutherian evolution. The relative conservatism of homology loop 1 (bovine residues 66-144) which has no known function is discussed 'gamma-Carboxyglutamic acid; (Gla) has been found in proteins unrelated to the plasma clotting factors; a bovine bone-matrix protein('osteocalcin') has been sequenced by Price et al. (Proc. natn. Acad Sci. USA 73: 3373-3375, 1976) but it shows no homology with prothrombin or factor X.