Characterization of zebrafish full-length prothrombin cDNA and linkage group mapping

In this paper, we report the complete cDNA sequence of zebrafish prothrombi n. The cDNA sequence predicts that zebrafish prothrombin is synthesized as a pre-proprotein consisting of a Gla domain, two kringle domains, and a two -chain protease domain. Zebrafish prothrombin is structurally very similar to human and other vertebrate prothrombins. Zebrafish and human prothrombin share 53% amino acid identity whereas zebrafish and hagfish prothrombin sh are 51% identity. Amino acid alignments of various prothrombins identified conservation of many of the functional/structural motifs suggesting that th e vertebrate prothrombins may have similar functions. The three-dimensional structure of prothrombin predicted by homology modeling also revealed that the prothrombin fragment 1 and the catalytic domain structures are well co nserved except for the insertion of an extra 7-amino-acid loop in the conne cting region (CR) between the Gla and kringle I domain of fragment 1. Linka ge analysis revealed that the prothrombin gene locus on linkage group 7 in zebrafish is syntenic to the human chromosome 11-prothrombin region suggest ing its preservation through evolution. The availability of this cDNA seque nce in zebrafish adds to our knowledge of the zebrafish hemostatic system a nd provides support for the view that similarities between zebrafish and ma mmalian coagulation exist, thus underscoring the relevance of the zebrafish model for studying human hemostasis. (C) 2000 Academic Press.