Gene organization of human protein C inhibitor, a member of SERPIN family proteins encoded in five exons.
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Hayashi T, Suzuki K
Gene organization of human protein C inhibitor, a member of SERPIN family proteins encoded in five exons.
Int J Hematol. 1993 Oct;58(3):213-24.
- PubMed ID
- 8148499 [ View in PubMed]
- Abstract
Protein C inhibitor (PCI), a plasma serine protease inhibitor, neutralizes activated protein C, which plays an important role in the regulation of blood coagulation. We determined the organization of the gene coding for this inhibitor. A human genomic phage DNA library was screened using the 32P-labeled protein C inhibitor cDNA as a probe and a phage genomic clone that contained the full length of the inhibitor gene, including the 5'- and 3'-flanking region, was isolated. The gene was characterized by restriction enzyme mapping, Southern blotting and sequencing all the coding parts as well as the 5'- and 3'-flanking regions. The protein C inhibitor gene spanned about 13 kilobase pairs and consisted of 5 exons and 4 introns as do the genes for human alpha 1-antitrypsin, alpha 1-antichymotrypsin, heparin cofactor II and rat angiotensinogen. All exon-intron boundaries agreed with the GT-AG rule. The 5'-flanking region contained no TATAA or CCAAT sequences, but contained the putative Sp-1 and AP-2 binding sites in the 5'-upstream region, which indicated promoter activity in human hepatoma cell line, HepG2, using the luciferase gene as a reporter gene and the polyadenylation site in the 3'-downstream region. A transcription initiation site was identified by primer extension analysis using template human liver poly(A)RNA. The length of the non-coding exon I of this inhibitor gene was similar to those of the other serine protease inhibitors as described above. These findings suggest that the protein C inhibitor gene evolved from a common ancestor gene of these serine protease inhibitors.