Title : Characterization of human blood
coagulation factor XII factor XII cDNA
Abstract :
- Prediction of the primary structure of factor XII and the tertiary structure of beta- factor XIIa
- A human liver cDNA library was screened by colony hybridization with two mixtures of synthetic oligodeoxyribonucleotides as probes
- These oligonucleotides encoded regions of beta- factor XIIa as predicted from the amino acid sequence
- Four positive clones were isolated that contained DNA coding for most of factor XII mRNA
- DNA sequence analysis of these overlapping clones showed that they contained DNA coding for part of an amino-terminal extension, the complete amino acid sequence of plasma factor XII , a TGA stop codon, a 3' untranslated region of 150 nucleotides, and a poly(A)+ tail
- The cDNA sequence predicts that plasma factor XII consists of 596 amino acid residues
- Within the predicted amino acid sequence of factor XII , we have identified three peptide bonds that are cleaved by kallikrein during the formation of beta- factor XIIa
- Comparison of the structure of factor XII with other proteins revealed extensive sequence identity with regions of tissue-type plasminogen activator (the epidermal growth factor-like region and the kringle region ) and fibronectin (type I and type II homologies)
- As the type II region of fibronectin contains a collagen-binding site , the homologous region in factor XII may be responsible for the binding of factor XII to collagen
- The carboxyl-terminal region of factor XII shares considerable amino acid sequence homology with other serine proteases including trypsin and many clotting factors
- A preliminary structural model of beta- factor XIIa is proposed based on the known high resolution x-ray diffraction structures of trypsin , chymo trypsin , and elastase