Thromb Haemost 1991; 66(01): 049-061
DOI: 10.1055/s-0038-1646373
Review Article
Schattauer GmbH Stuttgart

Protein S and C4b-Binding Protein: Components Involved in the Regulation of the Protein C Anticoagulant System

Björn Dahlbäck
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
25. Juli 2018 (online)

Summary

The protein C anticoagulant system provides important control of the blood coagulation cascade. The key protein is protein C, a vitamin K-dependent zymogen which is activated to a serine protease by the thrombin-thrombomodulin complex on endothelial cells. Activated protein C functions by degrading the phospholipid-bound coagulation factors Va and VIIIa. Protein S is a cofactor in these reactions. It is a vitamin K-dependent protein with multiple domains. From the N-terminal it contains a vitamin K-dependent domain, a thrombin-sensitive region, four EGF)epidermal growth factor (EGF)-like domains and a C-terminal region homologous to the androgen binding proteins. Three different types of post-translationally modified amino acid residues are found in protein S, 11 γ-carboxy glutamic acid residues in the vitamin K-dependent domain, a β-hydroxylated aspartic acid in the first EGF-like domain and a β-hydroxylated asparagine in each of the other three EGF-like domains. The EGF-like domains contain very high affinity calcium binding sites, and calcium plays a structural and stabilising role. The importance of the anticoagulant properties of protein S is illustrated by the high incidence of thrombo-embolic events in individuals with heterozygous deficiency. Anticoagulation may not be the sole function of protein S, since both in vivo and in vitro, it forms a high affinity non-covalent complex with one of the regulatory proteins in the complement system, the C4b-binding protein (C4BP). The complexed form of protein S has no APC cofactor function. C4BP is a high molecular weight multimeric protein with a unique octopus-like structure. It is composed of seven identical α-chains and one β-chain. The α-and β-chains are linked by disulphide bridges. The cDNA cloning of the β-chain showed the α- and β-chains to be homologous and of common evolutionary origin. Both subunits are composed of multiple 60 amino acid long repeats (short complement or consensus repeats, SCR) and their genes are located in close proximity on chromosome 1, band 1q32. Available experimental data suggest the β-chain to contain the single protein S binding site on C4BP, whereas each of the α-chains contains a binding site for the complement protein, C4b. As C4BP lacking the β-chain is unable to bind protein S, the β-chain is required for protein S binding, but not for the assembly of the α-chains during biosynthesis. Protein S has a high affinity for negatively charged phospholipid membranes, and is instrumental in binding C4BP to negatively charged phospholipid. This constitutes a novel mechanism for control of the complement system on phospholipid surfaces. Recent findings have shown circulating C4BP to be involved in yet another calcium-dependent protein-protein interaction with a protein known as the serum amyloid P-component (SAP). The binding sites on C4BP for protein S and SAP are independent. SAP, which is a normal constituent in plasma and in tissue, is a so-called pentraxin being composed of 5 non-covalently bound 25 kDa subunits. It is homologous to C reactive protein (CRP) but its function is not yet known. The specific high affinity interactions between protein S, C4BP and SAP suggest the regulation of blood coagulation and that of the complement system to be closely linked.

 
  • References

  • 1 Furie B, Furie BC. The molecular basis of blood coagulation. Cell 1988; 33: 505-18
  • 2 Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J. Biol. Chem. 1989; 264: 4743-46
  • 3 Stenflo J. The biochemistry of protein C. In Protein C and related proteins. (ed. Bertina RM. ) Churchill Livingstone, Longman Group UK: 1988. pp 21-54
  • 4 Mann KG, Jenny RJ, Krishnaswany S. Cofactor proteins in the assembly and expression of blood clotting enzyme complexes. Ann. Rev. Biochem. 1988; 57: 915-56
  • 5 Kane WH, Davie EW. Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood 1988; 71: 539-55
  • 6 DiScipio RG, Hermodson MA, Yates SG, Davie EW. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S. Biochemistry 1977; 16: 698-706
  • 7 DiScipio RG, Davie EW. Characterization of protein S, a γ-carboxy-glutamic acid containing protein from bovine and human plasma. Biochemistry 1979; 18: 899-904
  • 8 Stenflo J, Jönsson M. Protein S, a new vitamin K-dependent protein from bovine plasma. FEBS Lett. 1979; 101: 377-81
  • 9 Walker FJ. Regulation of activated protein C by a new protein. J. Biol. Chem. 1980; 255: 5521-24
  • 10 Comp PC, Nixon RR, Cooper MR, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J. Clin. Invest. 1984; 74: 2082-88
  • 11 Schwarz HP, Fischer M, Hopmeier P, Batard MA, Griffin JH. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64: 1297-1300
  • 12 Comp PC, Esmon CT. Recurrent thromboembolism in patients with a partial deficiency of protein S. N. Eng. J. Med. 1984; 311: 1525-28
  • 13 Kamiya T, Sugihara T, Ogata K, Saito H, Suzuki K, Nishioka J, Hashimoto S, Yamagata K. Inherited deficiency of protein S in a Japanese family with recurrent venous thrombosis: A study of three generations. Blood 1986; 67: 406-10
  • 14 Broekmans AW, Bertina RM, Reinalda-Poot J, Engesser L, Muller HP, Leeuw JA, Michiels JJ, Brommer EJP, Briet E. Hereditary protein S deficiency and venous thrombo-embolism. A study in three Dutch families. Thromb. Haemostas. 1985; 53: 273-77
  • 15 Bertina RM. Hereditary protein S deficiency. Haemostasis 1985; 15: 241-46
  • 16 Walker FJ. Regulation of bovine activated protein C by protein S: the role of the cofactor protein in species specificity. Thromb. Res. 1981; 22: 321-27
  • 17 Walker FJ. Regulation of activated protein C by protein S. The role of phospholipid in factor Va inactivation. J. Biol. Chem. 1981; 256: 11128-31
  • 18 Walker FJ. Interactions of protein S with membranes. Sem. Thromb. Hemostas. 1988; 14: 216-21
  • 19 Suzuki K, Nishioka J, Matsuda J, Murayama M, Hashimoto S. Protein S is essential for the activated protein C-catalyzed inactivation of platelet-associated factor Va. J. Biochem. 1984; 96: 455-60
  • 20 Harris KW, Esmon CT. Protein S is required for bovine platelets to support activated protein C binding and activity. J. Biol. Chem. 1985; 260: 2007-10
  • 21 Stern DM, Nawroth PP, Harris K, Esmon CT. Cultured bovine aortic endothelial cells promote activated protein C-protein S-mediated inactivation of factor Va. J. Biol. Chem. 1986; 261: 713-18
  • 22 Dahlbôck B, Wiedmer T, Esmon CT, Sims PJ. Assembly of protein S and protein C on platelet microparticles. Thromb. Haemostas. 1991 (abstract, in press)
  • 23 Sims PJ, Wiedmer T, Esmon CT, Weiss HJ, Shattil SJ. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. J. Biol. Chem. 1989; 264: 17049-57
  • 24 Dahlbôck B, Stenflo J. High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein. Proc. Natl. Acad. Sci. USA 1981; 78: 2512-16
  • 25 Law SKA, Reid KBM. Activation and control of the complement. In: Complement. (ed. Male D. ) IRL Press, Oxford, UK,: 1988. pp 9-27
  • 26 Scharfstein J, Ferreira A, Gigli I, Nussenzweig V. Human C4-binding protein. I. Isolation and characterization. J. Exp. Med. 1978; 148: 207-22
  • 27 Fujita T, Gigli I, Nussenzweig V. Human C4-binding protein. II. Role in proteolysis of C4b by C3b-inactivator. J. Exp. Med. 1978; 148: 1044-51
  • 28 Fujita T, Nussenzweig V. The role of C4-binding protein and β1H in proteolysis of C4b and C3b. J. Exp. Med. 1979; 150: 267-76
  • 29 Gigli I, Fujita T, Nussenzweig V. Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator. Proc. Natl. Acad. Sci. USA 1979; 76: 6596-6600
  • 30 Nagasawa S, Ichihara C, Stroud R. Cleavage of C4b by C3b inactivator: Production of a nicked form of C4b, C4b', as an intermediate cleavage product of C4b by C3b inactivator. J. Immunol. 1980; 125: 578-82
  • 31 Dahlbôck B. Purification of human C4b-binding protein and formation of its complex with vitamin K-dependent protein S. Biochem. J. 1983; 209: 847-56
  • 32 Dahlbôck B. Interaction between vitamin K-dependent protein S and the complement protein, C4b-binding protein. A link between coagulation and the complement system. Sem. Thromb. Hemostas. 1984; 10: 139-48
  • 33 Dahlbôck B, Smith CA, Müller-Eberhard HJ. Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b. Proc. Natl. Acad. Sci. USA. 1983; 80: 3461-65
  • 34 Dahlbôck B, Hildebrand B. Degradation of human complement component C4b in the presence of the C4b-binding protein-protein S complex. Biochem. J. 1983; 209: 857-63
  • 35 Dahlbôck B, Frohm B, Nelsestuen G. High affinity interaction between C4b-binding protein and vitamin K-dependent protein S in the presence of calcium. Suggestion of a Third Component in Blood Regulating the Interaction. J. Biol. Chem. 1990; 265: 16082-16087
  • 36 Schwalbe R, Dahlbôck B, Hillarp A, Nelsestuen G. Assembly of protein S and C4b-binding protein on membranes. J. Biol. Chem. 1990; 265: 16074-81
  • 37 Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplificaton of DNA with a thermostable DNA polymerase. Science 1988; 239: 487-91
  • 38 Barnum SR, Dahlbôck B. C4b-binding protein, a regulatory component of the classical pathway of complement, is an acute phase protein and is elevated in systemic lupus erythematosus. Complement and Inflammation 1990; 7: 71-77
  • 39 Comp PC, Doray D, Patton D, Esmon CT. An abormal distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504-8
  • 40 Dahlbôck B. Inhibition of protein Ca cofactor function of human and bovine proteins by C4b-binding protein. J. Biol. Chem. 1986; 261: 12022-27
  • 41 Bertina RM, van Wijngaarden A, Reinalda-Poot J, Poort SR, Bom VJJ. Determination of plasma protein S. The protein cofactor of activated protein C. Thromb. Haemostas. 1985; 53: 268-72
  • 42 Nishioka J, Suzuki K. Inhibition of cofactor activity of protein S by a complex of protein S and C4b-binding protein. J. Biol. Chem. 1990; 265: 9072-76
  • 43 Dahlbôck B. Purification of human vitamin K-dependent protein S and its limited proteolysis by thrombin. Biochem. J. 1983; 209: 837-46
  • 44 Fair DS, Marlar RA. Biosynthesis and secretion of factor VII, protein C, protein S, and the protein C inhibitor from a human hepatoma cell line. Blood 1986; 67: 64-70
  • 45 Fair DS, Marlar RA, Levin EG. Human endothelial cells synthesize protein S. Blood 1986; 67: 1168-71
  • 46 Stern D, Brett J, Harris K, Nawroth P. Participation of endothelial cells in the protein C - protein S anticoagulant pathway: The synthesis and release of protein S. J. Cell Biol. 1986; 102: 1971-78
  • 47 Ogura M, Tanabe N, Nishioka J, Suzuki K, Saito H. Biosynthesis and secretion of functional protein S by a human megakaryoblastic cell line (MEG-01). Blood 1987; 70: 301-6
  • 48 Malm J, Abrahamsson P-A, Dahlbôck B. Synthesis of vitamin K-dependent anticoagulant protein S by Leydig cells of human testis. 1991 (submitted)
  • 49 Dahlbôck B, Lundwall Å, Stenflo J. Primary structure of bovine vitamin K-dependent protein. Proc. Natl. Acad. Sci. USA 1986; 83: 4199-4203
  • 50 Lundwall Å, Dackowski W, Cohen E, Shaffer M, Mahr A, Dahlbôck B, Stenflo J, Wydro R. Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation. Proc. Natl. Acad. Sci. USA 1986; 83: 6717-20
  • 51 Hoskins J, Norman DK, Beckmann RJ, Long GL. Cloning and characterization of human liver cDNA encoding a protein S precursor. Proc. Natl. Acad. Sci. USA 1987; 84: 349-53
  • 52 Ploos van Amstel HK, van der Zanden AL, Reitsma PH, Bertina R. Human protein S cDNA encodes Phe-16 and Tyr 222 in the consensus sequences for the post-translational processing. FEBS Lett. 1987; 222: 186-90
  • 53 Malm J, Cohen E, Dackowski W, Dahlbôck B, Wydro R. Expression of completely γ-carboxylated and β-hydroxylated recombinant human vitamin-K-dependent protein S with full biological activity. Eur. J. Biochem. 1990; 187: 737-43
  • 54 Edenbrandt C-M, Lundvall Å, Wydro R, Stenflo J. Molecular analysis of the gene for vitamin K-dependent protein S and its pseudogene. Cloning and partial characterization. Biochemistry 1990; 29: 7861-68
  • 55 Ploos van Amstel HK, Reitsma PH, van der Logt PE, Bertina R. Intron-exon organization of the active human protein S gene PSα and its pseudogene PSβ; duplication and silencing during primate evolution. Biochemistry 1990; 29: 7853-61
  • 56 Schmidel DK, Tatro AV, Phelps LG, Tomczak JA, Long GL. Organization of the protein S genes. Biochemistry 1990; 29: 7845-52
  • 57 Ploos van Amstel JK, van der Zanden AL, Bakker E, Reitsma PH, Bertina RM. Two genes homologous with human protein S cDNA are located on chromosome 3. Thromb. Haemostas. 1987; 58: 982-87
  • 58 Watkins PC, Eddy R, Fukushima Y, Byers MG, Cohen EH, Dackowski WR, Wydro RM, Shows TB. The gene for protein S maps near the centromere of human chromosome 3. Blood 1988; 71: 238-41
  • 59 Long GL, Marshall A, Gardner JC, Naylor SL. Genes for human vitamin K-dependent plasma proteins C and S are located on chromosome 2 and 3, respectively. Somat. Cell Molec. Genet. 1988; 14: 93-98
  • 60 Gershagen S, Fernlund P, Lundwall Å. A cDNA coding for human sex hormone binding globulin. Homology to vitamin K-dependent protein S. FEBS Lett. 1987; 220: 129-35
  • 61 Baker ME, French FS, Joseph DR. Vitamin K-dependent protein S is similar to rat androgen-binding protein. Biochem. J. 1987; 243: 293-96
  • 62 Gershagen S, Lundvall A, Fernlund P. Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis. Nucleic Acid Res. 1989; 17: 9245-58
  • 63 Nelsestuen GL, Kisiel W, DiScipio RG. Interaction of vitamin K dependent proteins with membranes. Biochemistry 1978; 17: 2134-38
  • 64 Dahlbôck B, Lundwall A, Stenflo J. Localization of thrombin cleavage sites in the amino-terminal region of bovine protein S. J. Biol. Chem. 1986; 261: 5111-15
  • 65 Walker FJ. Regulation of vitamin K-dependent protein S. Inactivation with thrombin. J. Biol. Chem. 1984; 259: 10335-39
  • 66 Schwalbe RA, Ryan J, Stern DM, Kisiel W, Dahlbôck B, Nelsestuen GL. Protein structural requirements and properties of membrane binding by γ-carboxyglutamic acid-containing plasma proteins and peptides. J. Biol. Chem. 1989; 264: 20288-96
  • 67 Suzuki K, Nishioka J, Hashimoto S. Regulation of activated protein C by thrombin-modified protein S. J. Biochem. 1983; 94: 699-705
  • 68 Soriano-Garcia M, Park CH, Tulinsky A. Ravichandran KG, Skrzypczak-Jankun E. Structure of Ca2+ prothrombin fragment 1 including the conformation of the Gla domain. Biochemistry 1989; 28: 6805-10
  • 69 Mitchell CA, Hau L, Salem HH. Control of thrombin mediated cleavage of protein S. Thromb.. Haemostasis. 1986; 56: 151-54
  • 70 Drakenberg T, Fernlund P, Roepstorff P, Stenflo J. β-Hydroxyaspartic acid in vitamin K-dependent protein C. Proc. Natl. Acad. Sci. USA 1983; 80: 1802-6
  • 71 Fernlund P, Stenflo J. β-Hydroxyaspartic acid in vitamin K-dependent proteins. J. Biol. Chem. 1983; 258: 12509-12
  • 72 McMullen BA, Fujikawa K, Kisiel W. The occurrence of β-hydroxyaspartic acid in the vitamin K-dependent proteins. Biochem. Biophys. Res. Comm. 1983; 115: 8-14
  • 73 Carpenter G, Wahl MI. The epidermal growth factor family. In Handbook Exp. Pharmacol. (eds: Sporn MB, Roberts AB). Springer Bln. 1990; 25: 69-171
  • 74 Stenflo J, Lundwall A, Dahlbôck B. β-hydroxyasparagine in domains homologous to the epidermal growth factor precursor in vitamin K-dependent protein. Proc. Natl. Acad. Sci. USA 1987; 84: 368-72
  • 75 Przysiecki CT, Staggers JE, Rajmit HG, Musson DG, Stern AM, Bennett CD, Friedman PA. Occurrence of β-hydroxylated asparagine residues in non-vitamin K-dependent proteins containing epidermal growth factor-like domains. Proc. Natl. Acad. Sci. USA 1987; 84: 7856-60
  • 76 Stenflo J, àhlin A-K, Owen WG, Schneider WJ. β-hydroxyaspartic acid or β-hydroxyasparagine in bovine low density lipoprotein receptor and in bovine thrombomodulin.. J. Biol. Chem. 1988; 263: 21-24
  • 77 Arlaud GJ, Van Dorsellaer A, Bell A, Mancini M, Aude C, Gagnon J. Identification of erythro-β-hydroxyasparagine in the EGF-like domain of human C1r. FEBS Lett. 1987; 222: 129-34
  • 78 Kanzaki T, Olofsson A, MorÄn A, Wernstedt C, Hellman U, Miyazono K, Claesson-Welsh L, Heldin C-H. TGF-β1 binding protein: A component of the large latent complex of TGF-β1 with multiple repeat sequences. Cell 1990; 61: 1051-61
  • 79 Walker FJ. Characterization of a synthetic peptide that inhibits the interaction between protein S and C4b-binding protein. J. Biol. Chem. 1989; 264: 17645-48
  • 80 Persson E, Selander M, Linse S, Drakenberg T, àhlin A-K, Stenflo J. Calcium binding to the isolated β-hydroxyaspartic acid-containing epidermal growth factor-like domain of bovine factor X. J. Biol. Chem. 1989; 264: 16897-904
  • 81 àhlin A-K, Landes G, Bourdon P, Oppenheimer C, Wydro R, Stenflo J. β-Hydroxyaspartic acid in the first epidermal growth factor-like domain of protein C. J. Biol. Chem. 1988; 263: 19240-48
  • 82 Rees DJG, Jones JM, Handford PA, Walter SJ, Esnouf MP, Smith KJ, Brownlee GG. The role of β-hydroxyaspartate and adjacent carboxylate residues in the first EGF domain of human factor IX. EMBO J 1988; 7: 2053-61
  • 83 Dahlbôck B, Hildebrand B, Linse S. Novel type of very high affinity calcium-binding sites in β-hydroxy asparagine-containing epidermal growth factorlike domains in vitamin K-dependent protein S. J. Biol. Chem. 1990; 265: 18481-89
  • 84 Dahlbôck B, Hildebrand B, Malm J. Characterization of functionally important domains in vitamin K-dependent protein S using monoclonal antibodies. J. Biol. Chem. 1990; 265: 8127-35
  • 85 Wharton KA, Johansen KM, Xu T, Artavanis-Tsakonas S. Nucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 1985; 43: 567-81
  • 86 Knust E, Dietrich U, Tepass U, Bremer KA, Weigel D, Vôssin H, Campos-Ortega JA. EGF homologous sequences encoded in the genome of Drosophila melanogaster, and their relation to neurogenic genes. EMBO J. 1987; 6: 761-66
  • 87 Greenwald I. lin-12, A nematode homeotic gene, is homologous to a set of mammalian proteins that includes epidermal growth factor. Cell 1985; 43: 583-90
  • 88 Hursh DA, Andrews ME, Raff RA. A sea urchin gene encodes a polypeptide homologous to epidermal growth factor. Science 1987; 237: 1487-90
  • 89 Gray A, Dull T, Ullrich A. Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor. Nature 1983; 303: 722-25
  • 90 Tepass U, Theres C, Knust E. crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell 1990; 61: 787-99
  • 91 Montelione GT, Wüthrich K, Nice EC, Burgess AW, Scheraga HA. Solution structure of murine epidermal growth factor: determination of the polypeptide backbone chain-fold by nuclear magnetic resonance and distance genometry. Proc. Natl. Acad. Sci. USA 1987; 84: 5226-30
  • 92 Cooke RM, Wilkinson AJ, Baron M, Pastore A, Tappin MJ, Campbell ID, Gregory H, Sheard B. The solution structure of human epidermal growth factor. Nature 1987; 327: 339-41
  • 93 Selander M, Persson E, Stenflo J, Drakenberg T. H NMR assignment and secondary structure of the Ca2+-free form of the amino-terminal growth factor like domain in coagulation factor X. Biochemistry 1990; 29: 8111-18
  • 94 Davis CG, Goldstein JL, Südhof TC, Anderson RGW, Russell DW, Brown MS. Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. Nature 1987; 326: 760-65
  • 95 Stearns DJ, Kurosawa S, Esmon CT. Microthrombomodulin. Residues 310-486 from the epidermal growth factor precursor homology domain of thrombomodulin will accelerate protein C activation. J. Biol. Chem. 1989; 264: 3352-56
  • 96 Hyashi T, Zushi M, Yamamoto S, Suzuki K. Further localization of binding sites for thrombin and protein C in human thrombomodulin. J. Biol. Chem. 1990; 33: 20156-59
  • 97 Chung L P, Gagnon J, Reid KBM. Amino acid sequence studies of human C4b-binding protein: N-terminal sequence analysis and alignment of the fragments produced by limited proteolysis with chymotrypsin and the peptides produced by cyanogen bromide treatment. Mol. Immunol. 1985; 22: 427-35
  • 98 Chung LP, Bentley DR, Reid KBM. Molecular cloning and characterization of the cDNA coding for C4b-binding protein, a regulatory protein of the classical pathway of the human complement system. Biochem. J. 1985; 230: 133-41
  • 99 Dahlbôck B, Müller-Eberhard HJ. Ultrastructure of C4b-binding protein fragments formed by limited proteolysis using chymotrypsin. J. Biol. Chem. 1984; 259: 11631-34
  • 100 Nagasawa S, Unno H, Ichihara C, Koyama J, Koide T. Human C4b-binding protein, C4bp. Chymotryptic cleavage and location of the 48 kDa active fragment within C4bp. FEBS Lett. 1983; 164: 135-38
  • 101 Reid KBM, Day AJ. Structure-function relationships of the complement components. Immunol Today 1989; 10: 177-80
  • 102 Baron M, Norman DG, Campbell ID. Protein modules. TIBS 1991; 16: 13-17
  • 103 Reid KBM, Bentley DR, Campbell RD, Chung LP, Sim RB, Kristensen T, Tack BF. Complement system proteins which interacts with C3b or C4b. A superfamily of structurally related proteins. Immunol. Today 1986; 7: 230-34
  • 104 Kristensen T, DEustachio P, Ogata RT, Chung LP, Reid KBM, Tack BF. The superfamily of C3b/C4b-binding proteins.. Fed. Proc. 1987; 46: 2463-69
  • 105 Weis JJ, Toothaker LE, Smith JA, Weis JH, Fearon DT. Structure of the human B lymphocyte receptor for C3d and the Epstein-Barr virus and relatedness to other members of the family of C3/C4 binding proteins. J. Exp. Med. 1988; 167: 1047-66
  • 106 Moore MD, Cooper NR, Tack BF, Nemerow GR. Molecular cloning of the cDNA encoding the Epstein-Barr virus/C3d receptor (complement receptor type 2) of human lymphocytes. Proc. Natl. Acad. Sci. USA 1987; 84: 9194-98
  • 107 Lublin DM, Liszewski MK, Post TW, Arce MA, Le Beau MM, Rebentisch MB, Lemons RS, Seya T, Atkinson JP. Molecular cloning and chromocomal localization of human membrane cofactor protein (MCP). Evidence for inclusion in the multigene family of complement-regulatory proteins. J. Exp. Med. 1988; 168: 181-94
  • 108 Davitz MA, Low MG, Nussenzweig V. Release of decay-accelerating factor (DAF) from the cell membrane by phosphatidylinositol-specific phospholipase C (PIPLC). Selective modification of a complement regulatory protein. J. Exp. Med. 1986; 163: 1150-61
  • 109 Rey-Campos J, Rubinstein P, Rodriguez de Cordoba S. A physical map of the human regulator of complement activation gene cluster linking the complement genes CR 1, CR 2, DAF, and C4BP. J. Exp. Med. 1988; 167: 664-69
  • 110 Carroll MC, Alicot EM, Katzman PJ, Klickstein LB, Smith JA, Fearon DT. Organization of the genes encoding complement receptors type 1 and 2, decay-accelerating factor, and C4b-binding protein in the RCA locus on human chromosome 1. J. Exp. Med. 1988; 167: 1271-80
  • 111 Barlow PN, Baron M, Norman DG, Day AJ, Willis AC, Sim RB, Campbell ID. Secondary structure of a complement control protein module by two-dimensional H NMR,. Biochemistry 1991; 30: 997-1004
  • 112 Ziccardi RJ, Dahlbôck B, Müller-Eberhard HJ. Characterization of the interaction of human C4b-binding protein with physiological ligands. J. Biol. Chem. 1984; 259: 13674-79
  • 113 Chung LP, Reid KBM. Structural and functional studies on C4b-binding protein, a regulatory component of the human complement system. Biosci. Rep. 1985; 5: 855-65
  • 114 Fujita T, Kamato T, Tamura N. Characterization of functional properties of C4-binding protein by monoclonal antibodies. J. Immunol. 1985; 134: 3320-24
  • 115 Klickstein LB, Bartow TJ, Miletic V, Rabson LD, Smith JA, Fearon DT. Identification of distinct CRb and C4b recognition sites in the human C3b/C4b receptor (CR 1, CD 35) by deletion mutagenesis. J. Exp. Med. 1988; 168: 1699-1717
  • 116 Hillarp A, Dahlbôck B. Novel subunit in C4b-binding protein required for protein S binding. J. Biol. Chem. 1988; 263: 12759-64
  • 117 Hillarp A, Dahlbôck B. Cloning of cDNA coding for the β-chain of human complement component C4b-binding protein: Sequence homology with the a chain. Proc. Natl. Acad. Sci. USA. 1989; 87: 1183-87
  • 118 Andersson A, Dahlbôck B, Hansen C, Hillarp A, Levan G, Szpirer J, Szpirer C. Genes for C4b-binding protein α- and β-chains (C4BPA and C4BPB) are located on chromosome 1, band lq32, in humans and on chromosme 13 in rats. Som. Cell Molec. Gen. 1990; 16: 493-500
  • 119 Padro-Manuel F, Rey-Campos J, Hillarp A, Dahlbôck B, Rodriguez de Cordoba S. Human genes for the a and β-chains of complement C4b-binding protein are closely linked in a head-to-tail arrangement. Proc. Natl. Acad. Sci. USA 1990; 87: 4529-32
  • 120 Kristensen T, Ogata RT, Chung LP, Reid KBM, Tack BF. cDNA structure of murine C4b-binding protein, a regulatory component of the serum complement system. Biochemistry 1987; 26: 4668-74
  • 121 Perkins SJ, Chung LP, Reid KBM. Unusual ultrastructure of complement component C4b-binding protein of human complement by synchroton X-ray scattering and hydrodynamic analysis. Biochem. J. 1986; 233: 799-807
  • 122 Hillarp A, Hessing M, Dahlbôck B. Protein S binding in relation to the subunit composition of human C4b-binding protein. FEBS Lett. 1989; 259: 53-56
  • 123 Suzuki K, Nishioka J. Binding site for vitamin K-dependent protein S on complement C4b-binding protein. J. Biol. Chem. 1988; 263: 17034-39
  • 124 Hillarp A, Dahlbôck B. The protein S-binding site localized to the central core of C4b-binding protein. J. Biol. Chem. 1987; 262: 11300-307
  • 125 Skinner M, Cohen AS. Amyloid P component. Methods Enzymol. 1988; 163: 523-36
  • 126 Painter RH, De Escallou I, Massey A, Pinteric L, Stern SB. The structure and binding characteristics of serum amyloid protein (9.55 alpha 1-glycoprotein). Ann. N.Y. Acad. Sci. 1982; 389: 199-213
  • 127 De Beer FC, Baltz ML, Holford S, Feinstein A, Pepys MB. Fibronectin and C4-binding protein are selectively bound by aggregated amyloid P component. J Exp Med 1981; 154: 1134-49
  • 128 Baltz ML, De Beer FC, Feinstein A, Pepys MB. Calcium-dependent aggregation of human serum amyloid P component. Biochim. Biophys. Acta 1982; 701: 229-36
  • 129 Schwalbe RA, Dahlbôck B, Nelsestuen GL. Independent association of serum amyloid P component, protein S, and complement C4b with complement C4b-binding protein and subsequent association of the complex with membranes. J. Biol. Chem. 1990; 265: 21749-57
  • 130 Walker FJ. Properties of chemically modified protein S: Effect of the conversion of gamma-carboxy glutamic acid to gamma-methylene-glutamic acid on functional properties. Biochemistry 1986; 25: 6305-11
  • 131 Dahlbôck B, Fernlund P, Stenflo J. Protein C. New comprehensive biochemistry volume on blood coagulation. (eds: Zwaal FA, Hemker HC. ) Elsevier/North Holland: 1986. pp 285-303
  • 132 Hillarp A. Human C4b-binding protein. Studies on protein S binding, molecular forms and characterization of a novel subunit. Thesis,. Lund University, Sweden: 1990