Internal triplication in the structure of human ceruloplasmin.

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Abstract
Amino acid sequence analysis of the 67,000-dalton (67-kDal) fragment that is the amino-terminal half of human ceruloplasmin revealed internal triplication in the primary structure of the entire molecule. The 620 residues representing homologous domains of the 67-kDal fragment and of the 50-kDal and 19-kDal fragments that together comprise the carboxyl-terminal half of the molecule were compared. The polypeptide chain is divided into 3 covalently linked homologous segments, each of .apprx. 340 residues. All 3 homology units have .apprx. 30% identity in sequence, and each pair exhibits at least 40% identity. The statistical significance of the 3-fold internal duplication was established by computerized analysis of the sequence. These results and studies of the sites of limited proteolytic cleavage support a model for the ceruloplasmin molecule consisting of an alternating structure of 6 domains of 2 different kinds (or possibly 9 domains of 3 kinds). The 3-fold internal homology suggests that the ceruloplasmin molecule evolved by tandem triplication of ancestral genes.