The human tissue plasminogen activator gene

The nucleotide sequence of the human tissue plasminogen activator (t-PA) gene has been established. A total of 36,594 base pairs (bp) was sequenced; this included 32,720 bp from the site of initiation of transcription to the polyadenylation site, in addition to 3,530 and 344 bp of 5' and 3' flanking DNA, respectively. Thirteen intervening sequences divide the gene into 14 coding regions; the size range for exons is 43-914 bp, while that for introns is 111-14,257 bp. The gene and 5' flanking region contain 28 copies of Alu repetitive DNA and a single KpnI repeat. The transcription initiation site was identified by S1 nuclease, exonuclease VII, and primer extension analysis as an A residue; “TATA” and “CAAT” boxes are located in the expected positions upstream of this proposed site. Results of the analysis of the gene sequence and its comparison with data banks are described. The protein and gene structures of tissue and urokinase plasminogen activator are compared; based on these features the evolutionary relationship of the two human plasminogen activators appears to be close.