STRUCTURE OF THE HUMAN UROKINASE RECEPTOR GENE AND ITS SIMILARITY TO CD59 AND THE LY-6 FAMILY

Urokinase plasminogen activator receptor (uPAR) gene expression has be en implicated in many important biological processes including cell in vasiveness and migration. The uPAR gene was cloned from a human genomi c library by hybridization with a uPAR cDNA. The complete structure of the human uPAR gene, including a 21.23-kb transcription unit with 204 bp 5' and 239 bp 3' flanking sequences, was determined by comparison with the uPAR cDNA sequence. The uPAR gene is composed of seven exons and six introns. The seven exons of 101, 111, 144, 162, 135, 147 and 5 63 bp are separated by six introns of approximately 2.04, 2.62, 8.42, 0.906, 3.10 and 2.78 kb. Exons 1-7 encode 19, 37, 48, 54, 45, 49 and 8 3 amino acid residues, respectively. A CpG-rich island and sequences r elated to the transcription factors AP-1, AP-2, c-Jun and MF kappa-B a re present, but no potential TATA or CAAT boxes were found in the prox imal 5' region of the uPAR gene. Comparison of the exon organization o f the uPAR gene with that of human CD59 and murine Ly-6 reveals simila rity to all three domains encoded by the uPAR exons (2+3), (4+5) and ( 6+7). These data enable elucidation of the mechanisms involved in regu lation of the uPAR gene expression and provide further evidence that t he uPAR gene belongs to the Ly-6 superfamily.