Radtke K P, Greengard J S, Fernández J A, Villoutreix B O, Griffin J H
Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA, USA.
Thromb Haemost. 1996 Jan;75(1):62-9.
cDNAs for protein C inhibitor (PCI), prepared from human liver RNA, contained two forms of PCI, designated PCIA and PCIB. While PCIA is identical to the published PCI sequence, PCIB differs in 4 of 1221 bp and two amino acids, A36V and K86E. Frequencies for the PCIB allele, determined from genomic DNA, differed among ethnic groups. Frequency distribution and historical migration of modern man suggest that PCIA arose from the PCIB allele. Antigen levels in plasma homozygous for PCIA or PCIB equalled that of pooled normal plasma. K86E in PCIB causes a charge alteration in helix D which is likely involved in heparin binding in antithrombin III but not likely involved in glycosaminoglycan binding in PCI. Kinetic studies showed that plasmas homozygous for PCIA and PCIB are similar in their APC inhibiting properties and in their heparin sensitivity, consistent with the idea that helix D in PCI is not involved in heparin binding.
从人肝RNA制备的蛋白C抑制剂（PCI）的cDNA包含两种形式的PCI，分别命名为PCIA和PCIB。虽然PCIA与已发表的PCI序列相同，但PCIB在1221个碱基对中有4个不同，并且有两个氨基酸不同，即A36V和K86E。从基因组DNA确定的PCIB等位基因频率在不同种族群体中有所不同。现代人类的频率分布和历史迁徙表明PCIA起源于PCIB等位基因。PCIA或PCIB纯合子血浆中的抗原水平与混合正常血浆的抗原水平相当。PCIB中的K86E导致螺旋D中的电荷改变，这可能与抗凝血酶III中的肝素结合有关，但不太可能与PCI中的糖胺聚糖结合有关。动力学研究表明，PCIA和PCIB纯合子血浆在其活化蛋白C抑制特性和肝素敏感性方面相似，这与PCI中的螺旋D不参与肝素结合的观点一致。
