Genomic structure and chromosomal localization of the human hepatocyte growth factor activator inhibitor type 1 and 2 genes.
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) are recently discovered Kunitz-type serine protease inhibitors which can be purified and cloned from human stomach cancer cell line MKN45 as specific inhibitors against hepatocyte growth factor activator (HGFA). HAI-2 was identical with the protein originally reported as placental bikunin. Both proteins contain two Kunitz inhibitor domains (KDs), of which the first domain (KD1) is mainly responsible for the inhibitory activity against HGFA, and are expressed ubiquitously in various tissues. In this study, we cloned the genes coding for these two structurally similar proteins by screening of human genomic bacterial artificial chromosome (BAC) library and their genomic structures were compared. HAI-1 and -2 genes consist of 11 and 8 exons spanning 12 kbp and 12.5 kbp, respectively. Three exons were inserted between KD1 and KD2 of each gene, of which the middle one was the low-density lipoprotein (LDL) receptor-like domain (HAI-1) and the testis specific exon (HAI-2). Apparently homologous regions between HAI-1 and -2 were not found in 5'-flanking region and neither TATA nor CAAT box was present. The genes were mapped to chromosome 15q15 (HAI-1) and 19q13.11 (HAI-2). These results suggested that although HAI-1 and -2 genes might be derived from same ancestor gene, they acquired distinctive in vivo roles during their evolution.
Itoh
H
H
Second Department of Pathology, Miyazaki Medical College, Miyazaki, Japan. hitoh@post.miyazaki-med.ac.jp
Yamauchi
M
M
Kataoka
H
H
Hamasuna
R
R
Kitamura
N
N
Koono
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005796:Genes; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D053491:Proteinase Inhibitory Proteins, Secretory; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014360:Trypsin Inhibitor, Kunitz Soybean
D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; C109149:SPINT1 protein, human; C109148:SPINT2 protein, human; D014360:Trypsin Inhibitor, Kunitz Soybean