MOLECULAR-CLONING, SEQUENCE-ANALYSIS, AND CHROMOSOMAL LOCALIZATION OFTHE HUMAN PROTEASE INHIBITOR-4 (KALLISTATIN) GENE (PI4)

The gene encoding human protease inhibitor 4 (kallistatin; gene symbol PI4), a novel serine proteinase inhibitor (serpin), has been isolated and completely sequenced. The kallistatin gene is 9618 bp in length a nd contains five exons and four introns. The structure and organizatio n of the kallistatin gene are similar to those of the genes encoding a lpha(1)-antichymotrypsin, protein C inhibitor, and alpha(1)-antitrypsi n. The kallistatin gene is also similar to the genes encoding rat and mouse kallikrein-binding proteins. The first exon of the kallistatin g ene is a noncoding 89-bp fragment, as determined by primer extension. The fifth exon, which contains 308 bp of noncoding sequence, encodes t he reactive center of kallistatin. In the 5'-flanking region of the ka llistatin gene, 1125 bp have been sequenced and a consensus promoter s egment with potential transcription regulatory sites, including CAAT a nd TATA boxes, an AP-2 binding site, a GC-rich region, a cAMP response element, and an AP-1 binding site, has been identified within this re gion. The kallistatin gene was localized by in situ hybridization to h uman chromosome 14q31-q32.1, close to the serpin genes encoding alpha( 1)-antichymotrypsin, protein C inhibitor, alpha(1)-antitrypsin, and co rticosteroid-binding globulin. In a genomic DNA Southern blot, kallist atin-related genes were identified in monkey, mouse, rat, bovine, dog, cat, and a ground mole. The patterns of hybridization revealed clues of human serpin evolution. (C) 1994 Academic Press, Inc.