Figure 2.

The human Factor H–CFHR gene cluster and the FHR, Factor H protein family. The human Factor H–CFHR gene cluster includes the Factor H gene and the five CFHR genes, which are located on chromosome 1q32. Left side: The CFHR genes are positioned downstream of the Factor H gene (bottom) and are arranged in the order CFHR3, CFHR1, CFHR4, CFHR2, and CFHR5. The human CFHR gene cluster includes interspersed duplicated regions, or segmental duplication elements, which have a high sequence identity and are shown as colored bars below the gene structure. Middle segment: Proteins. Domain organization of the secreted FHR proteins and of Factor H gene products FHL1 and Factor H. Each SCR domain is indicated and the domains of each protein are consecutively numbered. Attached carbohydrate side chains are shown above by the tree-like structure. Constitutively attached carbohydrate side chains have black lines, and facultatively attached carbohydrates have gray lines. The N-terminal multimerization domains of FHR1, FHR2, and FHR5 represented by two SCRs are filled with dashed lines. The C-terminal surface-binding regions of FHR1 and the surface-binding regions of Factor H and FHL1 are shown with a stippled pattern. FHR1: L₂₉₀A₂₉₆ indicates the two FHR1-specific residues, which differ from that of Factor H. Bottom: The human Factor H gene encodes two fluid-phase C3 convertase inhibitors, FHL1 and Factor H. The complement regulatory region is located in SCRs 1–4, is shown by the orange patterns, and is shared by FHL1 and Factor H. The C-terminal recognition regions, i.e., SCRs 6–7 (FHL1/Factor H) and SCRs 19–20 (Factor H), are shown by blue patterns. The Factor H–specific two amino acids S₁₁₉₁V₁₁₉₆ in the most C-terminal recognition region are shown in the box below SCR 20. FHL1 has a unique six–amino-acid extension that follows SCR 7. Right side: Identified major functions of each FHR protein and of Factor H and FHL1.