Organization of the human protein S genes.

Human genomic clones that span the entire protein S expressed gene (PS{alpha}) and the 3{prime} two-thirds of the protein S pseudogene (PS{beta}) have been isolated and characterized. The PS{alpha} gene is greater than 80 kilobases in length and contains 14 introns and 15 exons, as well as 6 repetitive Alu sequences. Exons I and XV contain 112 and 1,139 bp 5{prime} and 3{prime} noncoding segments in addition to the amino and carboxyl termini, respectively. Exons I-VIII encode protein segments that are homologous to the vitamin K dependent clotting proteins and are bounded by introns whose position and type are identical with other members of this protein family. Exons IX-XV encode protein segments homologous to sex hormone binding globulin (SHBG) and are bounded by introns of identical type and position as in the SHBG gene. Genomic clones for the PS{beta} gene cover a distance of greater than 55 kilobases and contain segments corresponding to amino acids 46-635 of the mature protein and the 1.1-kb 3{prime} noncoding region of the cDNA. The presence of multiple base changes in the coding portion of this gene, resulting in termination codons and frame shifts, suggests that it is a pseudogene. Comparison of DNA sequences formore » the two genes reveals 97% identity for coding and 3{prime} noncoding, and 95.4% for intronic regions, suggesting divergence of the two genes is a relatively recent event.« less