Subscribe to RSS
DOI: 10.1055/s-0038-1650222
A Two-Allele Polymorphism in Protein C Inhibitor with Varying Frequencies in Different Ethnic Populations
Publication History
Received 14 July 1994
Accepted after resubmission 19 September 1995
Publication Date:
10 July 2018 (online)
Summary
cDNAs for protein C inhibitor (PCI), prepared from human liver RNA, contained two forms of PCI, designated PCI*A and PCPB[ 1 ]. While PCI*A is identical to the published PCI sequence, PCPB differs in 4 of 1221 bp and two amino acids, A36V and K86E. Frequencies for the PCI*B allele, determined from genomic DNA, differed among ethnic groups. Frequency distribution and historical migration of modem man suggest that PCI*A arose from the PCI*B allele. Antigen levels in plasma homozygous for PCI*A or PCI*B equalled that of pooled normal plasma. K86E in PCI*B 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 PCI*A and PCPB 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
1 The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) U35464
-
References
- 1 Marlar RA, Griffin JH. Deficiency of protein C inhibitor in combined factor V/VIII deficiency disease. J Clin Invest 1980; 66: 1186-1189
- 2 Suzuki K, Nishioka J, Hashimoto S. Protein C inhibitor: Purification from human plasma and characterization. J Biol Chem 1983; 258: 163-168
- 3 Radtke K-P, Stief TW, Heimburger N. A new and simple isolation procedure for human protein C inhibitor. Biol Chem Hoppe Seyler 1988; 369: 965-974
- 4 Laurell M, Carlson TH, Stenflo JA. Monoclonal antibodies against the heparin-dependent protein C inhibitor suitable for inhibitor purification and assay of inhibitor complexes. Thromb Haemost 1988; 60: 334-339
- 5 Pratt CW, Macik BG, Church FC. Protein C inhibitor. Purification and proteinase reactivity. Thromb Res 1989; 53: 596-602
- 6 Suzuki K, Deyashiki Y, Nishioka J, Kurachi K, Akiras M, Yamamoto S, Hashimoto S. Characterization of a cDNA for human protein C inhibitor: A new member of the plasma serine protease inhibitor superfamily. J Biol Chem 1987; 262: 611-616
- 7 Heeb MJ, España F, Griffin JH. Inhibition and complexation of activated protein C by two major inhibitors in plasma. Blood 1989; 73: 446-454
- 8 España F, Berrettini M, Griffin JH. Purification and characterization of plasma protein C inhibitor. Thromb Res 1989; 55: 369-384
- 9 Laurell M, Christensson A, Abrahamsson P, Stenflo J, Lilja H. Protein C inhibitor in human body fluids. Seminal plasma is rich in inhibitor antigen deriving from cells throughout the male reproductive system. J Clin Invest 1992; 89: 1094-1101
- 10 Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 1984; 12: 387-395
- 11 Radtke K-P, Fernandez JA, Villoutreix B, Greengard JS, Griffin JH. Characterization of a cDNA for rhesus monkey protein C inhibitor. Evidence for N-terminal involvement in heparin stimulation. Thromb Haemost 1995; 74: 1079-1087
- 12 Radtke K-P, Fernández JA, Greengard JS, Tang WW, Wilson CB, Loskut-off DJ, Scharrer I, Griffin JH. Protein C Inhibitor is Expressed in Tubular Cells of Human Kidney. J Clin Invest 1994; 94: 2117-2124
- 13 Johnson CS, Tegos C, Beutler E. α-Thalassemia. Prevalence and hematologic findings in American Blacks. Arch Intern Med 1995; 142: 1280-1282
- 14 Lindblom B, Holmlund G. Rapid DNA purification for restriction fragment length polymorphism analysis. Gene Anal Tech 1988; 5: 097-101
- 15 Kuhn LA, Griffin JH, Fisher CL, Greengard JS, Bouma BN, España F, Tainer JA. Elucidating the structural chemistry of glycosaminoglycan recognition by protein C inhibitor. Proc Natl Acad Sci USA 1990; 87: 8506-8510
- 16 Insightll. Delphi, Homology, Discover. Anonymous ed San Diego: CA: Biosym. Technologies, Inc; 1993
- 17 Bernstein FC, Koetzle TF, Williams GJB, Meyer Jr EF, Brice JD, Rodgers JR, Kennard O, Shimanouchi T, Tasmui M. The protein data bank: A computer-based archival file for macromolecular structures. J Mol Biol 1977; 112: 535-542
- 18 Gilson M, Sharp K, Honig B. Calculating the electrostatic potential for molecules in solution. J Comp Chem 1987; 9: 327-335
- 19 Heeb MJ, Schwarz HP, White T, Lämmle B, Berrettini M, Griffin JH. Im-munoblotting studies of the molecular forms of protein C in plasma. Thromb Res 1988; 52: 33-43
- 20 España F, Griffin JH. Determination of functional and antigenic protein C inhibitor and its complexes with activated protein C in plasma by ELISAs. Thromb Res 1989; 55: 671-682
- 21 Meijers JCM, Chung DW. Evidence for a Glycine Residue at Position 316 in Human Protein C Inhibitor. Thromb Res 1990; 59: 389-393
- 22 Meijers JCM, Chung DW. Organization of the gene coding for human protein C inhibitor (plasminogen activator inhibitor-3). J Biol Chem 1991; 266: 15028-15034
- 23 Meijers JCM, Kanters DHAJ, Vlooswijk RAA, Vlooswijk HE, van Erp HE, Hessing M, Bouma BN. Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry 1988; 27: 4231-4237
- 24 Laurell M, Stenflo JA. Protein C inhibitor from human plasma: Characterization of native and cleaved inhibitor and demonstration of inhibitor complexes with plasma kallikrein. Thromb Haemost 1989; 62: 885-891
- 25 España F, Estellés A, Griffin JH, Aznar J. Interaction of plasma kallikrein with protein C inhibitor in purified systems and in plasma. Thromb Haemost 1991; 65: 46-51
- 26 Stief WT, Radtke K-P, Heimburger N. Inhibition of urokinase by protein C inhibitor (PCI): Evidence for identity of PCI and plasminogen activator inhibitor 3 (PAI3). Biol Chem Hoppe Seyler 1987; 368: 1427-1433
- 27 España F, Gilabert J, Estellés A, Romeu A, Aznar J, Cabo A. Functionally active protein C inhibitor/plasminogen activator inhibitor-3 (PCI/PAI-3) is secreted in seminal vesicles, occurs at high concentrations in human seminal plasma and complexes with prostate-specific antigen. Thromb Res 1991; 64: 309-320
- 28 Andrews P. Cold Spring Harbor Symposia on Quantitative Biology, Volume LI. In: Cold Spring Harbor Laboratory Anonymous ed 1986: 419-428
- 29 Cavalli-Sforza LL, Menozzi P, Piazza A. The history and geography of human genes. Anonymous, ed Princeton, New Jersey: Princeton University Press; 1994
- 30 Jordan RE, Oosta GM, Gardner WT, Rosenberg RD. The kinetics of hemostatic enzyme-antithrombin interactions in the presence of low molecular weight heparin. J Biol Chem 1980; 255: 10081-10090
- 31 Lindahl U, Bäckström G, Thunberg L. The antithrombin-binding sequence in heparin. J Biol Chem 1983; 258: 9826-9830
- 32 Tollefsen DM, Majerus DW, Blank MK. Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. J Biol Chem 1982; 257: 2162-2169
- 33 Huber R, Carrell RW. Implications of the three-dimensional structure of α1-antitrypsin for structure and function of serpins. Biochemistry 1989; 28: 8951-8966
- 34 Koide T, Odani S, Takahashi K, Ono T, Sakuragawa N. Antithrombin III toyama: Replacement of arginine-47 by cysteine in hereditary abnormal antithrombin III that lacks heparin-binding ability. Proc Natl Acad Sci USA 1984; 81: 289-293
- 35 Owen MC, Borg JY, Soria C, Soria J, Caen J, Carrell RW. Heparin binding defect in a new antithrombin III variant: Rouen, 47 Arg to His. Blood 1987; 69: 1275-1279
- 36 Borg JY, Owen MC, Soria C, Soria J, Caen J, Carrell RW. Proposed heparin binding site in antithrombin based on arginine 47. A new variant Rouen-II, 47 Arg to Ser. J Clin Invest 1988; 81: 1292-1296
- 37 Pratt CW, Church FC. Heparin binding to protein C inhibitor. J Biol Chem 1992; 267: 8789-8794
- 38 Jeppsson J. Amino acid substitution Glu→Lys in α1-antitrypsin PiZ. FEBS Lett 1976; 65: 195-197
- 39 Curiel DT, Chytil A, Courtney M, Crystal RG. Serum ar-antitrypsin deficiency associated with the common S-type (Glu264→Val) mutation results from intracellular degradation of a,-antitrypsin prior to secretion. J Biol Chem 1989; 264: 10477-10486
- 40 Lomas DA, Evans DL, Finch JT, Carrell RW. The mechanism of Z α1-antitrypsin accumulation in the liver. Nature 1992; 357: 605-607
- 41 Hermans JM, Jones R, Stone SR. Rapid inhibition of the sperm protease ac-rosin by protein C inhibitor. Biochemistry 1994; 33: 5440-5444