Structural organization and chromosomal localization of the human hepatocyte growth factor activator gene - Phylogenetic and functional relationship with blood coagulation factor XII, urokinase, and tissue-type plasminogen activator

The organization and structure of the gene coding for hepatocyte growth fac tor activator (HGFA) have been determined by isolation of unique clones fro m a human genomic library. These clones were characterized by restriction m apping, Southern blotting and DNA sequencing. The complete sequence of the gene was determined and found to span about 7.5 kilobases of DNA and consis t of 14 exons separated by 13 introns. The coding region of HGFA consists o f multiple putative domains that are homologous to those observed in blood coagulation factor XII (FXII). These regions were found as separate exons i n the gene, and the exon/intron arrangement was similar to that of FXII, su ggesting that the genes for HGFA and FXII have arisen through gene duplicat ion events from a common ancestral gene. The major transcription initiation site is located 75 bp upstream of the translational start codon. The gene was mapped to chromosome 4p16, using spot-blot hybridization on sorted chro mosomes and fluorescence in situ hybridization on metaphase chromosome spre ads. The phylogenetic and functional relationships between HGFA and FXII as well as urokinase and tissue-type plasminogen activator are discussed.