Open AccessThe organization of the human‐plasminogen‐activator‐inhibitor‐1 gene
Author(s) -
STRANDBERG Leif,
LAWRENCE Daniel,
NY Tor
Publication year - 1988
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1988.tb14320.x
Subject(s) - serpin , intron , gene , biology , exon , 5' flanking region , consensus sequence , coding region , genetics , plasminogen activator , microbiology and biotechnology , promoter , tata box , plasminogen activator inhibitor 1 , serine protease , serine proteinase inhibitors , peptide sequence , gene expression , protease , biochemistry , enzyme
Plasminogen activator inhibitor 1 (PAI‐1) is a member of the serine protease inhibitor super family (SERPINS) which is thought to play an integral role in the control of plasminogen activation. PAI‐1 inhibits both tissue‐type plasminogen activator and urokinase‐type plasminogen activator and may therefore be implicated in the control of various physiological processes. We have isolated the PAI‐1 gene including its 5′‐flanking sequence. The gene was characterized by restriction enzyme analysis, Southern blotting and DNA sequencing of all the coding parts as well as the 5′‐flanking region. The PAI‐1 gene contains nine exons and eight introns distributed over approximately 12.3 kb of DNA. All exon/intron boundaries agree with the ‘GT‐AG’ rule. To characterize the presumptive promoter region, 800 bp of the 5′‐flanking region was sequenced and potential binding sites for transacting transcriptional factors were localized. The transcription initiation site was identified by S1 protection experiments and is located 25 base pairs downstream of a TATA consensus sequence. By aligning the gene structure of PAI‐1 and four other SERPINS and extrapolating a general tertiary structure to these SERPINS, we find that most introns map between subdomain structures of the proteins. Evidence is presented supporting an intron loss model for the evolution of the SERPIN family.