Revised Manuscript Received July 23, 1991 abstract: A human genomic DNA library was screened by using conditions of reduced stringency with a bovine cDNA probe coding for the kringle domains in prothrombin in order to isolate the human pro-thrombin gene. Twelve positives were identified, three of which coded for prothrombin (Degen & Davie, 1987). Phage L5 was characterized in more detail because of its strong hybridization to the cDNA probe and its unique restriction map compared to the gene coding for human prothrombin. The gene in L5 was sequenced andfound to code for a kringle-containing protein. A human liver cDNA library was screened by using a genomic probe from the gene in L5. cDNAs were isolated that contained sequence identical with regions in the gene in L5. Comparison of the cDNA with the gene indicated that the gene in L5 was composed of 18 exons separated by 17 intervening sequences and is 4690 bpin length. Exons ranged in size from 36 to 242 bp in length while intervening sequences ranged from 77 to 697 bp in length. The putative protein encoded by the gene in L5 contains four kringle domains followed by a serine protease-like domain. This domain structure is identical with that found in hepatocyte growth factor (HGF), although the two proteins are only about 50% identical. On the basis of the similarity of the protein encoded by L5 and HGF, we propose that the putative L5 protein be tentatively called HGF-like protein until a function is identified. The DNA sequence of the gene and cDNA and its translated amino acid sequence were compared against GenBank and NBRF databases. Sequences homologous to DNF15S1 and DNF15S2, human DNF15S2 lung mRNA, and rat acyl-peptide hydrolase were identified in exon 17 to the 3'end of the characterized sequence for the gene. From our results, it is apparent that the gene coding for human HGF-like protein is located at the DNF15S2 locus on human chromosome 3 (3p21). The gene for acyl-peptide hydrolase is 444 bp downstream of the gene coding for HGF-like protein, but on the complementary strand. The DNF15S2 locus has been proposed to code for one or more tumor suppressorgenes since this locus is deleted in DNA from small cell lung carcinoma, other lungcancers, renal cell carcinoma, and von Hippel-Lindau syndrome. e amino-terminal noncatalytic region of theproteases involved in blood coagulation and fibrinolysis contains several types of domains that are responsible for the regulatory function of these proteins, a feature that distinguishes them from the digestive proteases trypsin and chymotrypsin (Davie et al., 1986; Furie & Furie, 1988). These regulatory regions are organized with various combinations of domains that in-clude kringles, epidermal growth factor-like structures, finger structures, vitamin K dependent calcium-binding regions, and apple structures (McMullen et al., 1991). These domains appear to be essential for the biological specificity of the enzymatic portion of the molecule. Kringle-containing proteins that have been identified were until recentlyconfined to plasma proteins that functioned in either blood coagulation or fibrinolysis. These included factor XII, prothrombin, tissue plasminogen activator (t-PA), 1 uro-kinase (u-PA), and plasminogen with one, two, two, one, and