Molecular cloning of the cDNA coding for human C1 inhibitor.

A clone coding for the precursor form of C1 inhibitor has been isolated from a human liver cDNA library constructed in lambda gt11. This clone contains a cDNA insert of 1777 nucleotides, which includes 63 nucleotides coding for a signal sequence of 21 amino acids, 1434 nucleotides coding for the mature protein of 478 amino acids, a stop codon of TGA, and 265 nucleotides of the 3'-noncoding sequence followed by a poly(A) tail of 12 nucleotides. The predicted amino acid sequence of mature C1 inhibitor contains a unique region (positions 43 to 97) of 14 tandemly repeated copies of the tetrapeptide Gln-Pro-Thr-Thr and variants thereof. The carboxy-terminal sequence (positions 98 to 478) comprises the typical structural elements of a serine proteinase inhibitor (serpin). These findings indicate that C1 inhibitor is unique among the known members of the serpin superfamily due to the presence of an extra-domain of highly repetitive structure located at the amino-terminus of the inhibitor.