The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains.

Abstract

A genomic clone carrying the human tissue-type plasminogen activator (t-PA) gene was isolated from a cosmid library, and the gene structure was elucidated by restriction mapping, Southern blotting and DNA sequencing. The cosmid contained all the coding parts of the mRNA, except for the first 58 bases in the 5'' end of the mRNA, and had a total length of > 20 kilobases. It was seperated into at least 14 exons by at least 13 introns, and the exons seemed to code for structural or functional domains. The signal peptide, the propeptide and the domains of the H chain, including the regions homologous to growth factors, and to the finger structure of fibronectin, are all encoded by seperate exons. The 2 kringle regions of t-PA were both coded for by 2 exons and were cleaved by introns at identical positions. The region coding for the L chain, comprising the serine protease part of the molecule was split by 4 introns, revealing a gene organization similar to other serine proteases.