Molecular cloning and sequencing of cDNA encoding plasma countertrypin, a member of mammalian fetuin family, from the Mongolian gerbil, Meriones unguiculatus.

Complementary DNA clones coding for countertrypin were isolated from a liver cDNA library of the Mongolian gerbil, and sequenced. They contained one open reading frame encoding 348 amino acid residues, which were assigned to consist of an 18-residue signal peptide and a 330-residue mature protein. The amino acid sequence was about 74% identical with mouse countertrypin and rat fetuin, 60% with bovine fetuin, and 55% with human alpha2HS glycoprotein, indicating that this protein belongs to the mammalian fetuin family. The members of this family are known to consist of three domains, i.e., two tandemly arranged cystatin domains (D1 and D2) and an unrelated domain (D3) located at the C-terminal region. When compared with the other members of this family, D3, especially its N-terminal half, varies greatly with deletion or insertion as well as nucleotide substitutions even among three rodent species, i.e., gerbil, rat, and mouse. The sequence comparison also suggests that the conformation of human alpha2HS glycoprotein differs greatly from that of other members of this family. A molecular phylogenetic tree of 7 members, constructed on the basis of the synonymous substitution rate of D1 and D2, shows that the gerbil gene diverged prior to the separation of mouse and rat.