Human Genes for the α and β Chains of Complement C4b-Binding Protein are Closely Linked in a Head-to-Tail Arrangement

C4b-binding protein (C4BP) is an important component in the regulation of the complement system and also binds the anticoagulant vitamin K-dependent protein S. These activities are performed by distinct, although structurally related, polypeptides of 70 kDa (α chain) and 45 kDa (β chain), respectively. In this report we have investigated the genetic relationships between these polypeptides. Using pulsed field gel electrophoresis analysis we demonstrate that the genes coding for the α (C4BPα) and β (C4BPβ) chains are closely linked within the regulator of complement activation gene cluster. In addition, we have determined that the 3' end of the C4BPβ gene lies 3.5-5 kilobases from the 5' end of the C4BPα gene. These findings support the concept that the C4BPα and C4BPβ genes are the result of a gene duplication event.