Complement Factor I (CFI)

Complement factor I (CFI), also known as C3b/C4b inactivator, is a protein that is encoded by the CFI gene. It was firstly identified in 1966 in guinea pig serum and was considered as an enzyme associated with the physiological degradation of the major plasma complement protein C3. Later, it was also indicated to function in the physiological breakdown of the human complement protein C4. By the early 1980s, CFI was revealed to act in the cleavage of the complement protein fragment C3b to form iC3b, and the cleavage of C4b to form C4c plus C4d. The CFI plays an important role in complement activation by cleaving cell-bound or fluid phase C3b and C4b.

CFI is produced primarily in the liver, monocytes, fibroblasts, keratinocytes, and endothelial cells. The factor I encoded by the CFI gene is a 66 kDa polypeptide chain with N-linked glycans at 6 positions. After that, the protein cleaved by furin to mature factor I protein which is a heterodimer consisting of a disulfide-linked heavy chain (residues 19-335, 51 kDa) and light chain (residues 340-583, 37 kDa). The factor I heavy chain acts as an inhibitor in maintaining the enzyme inactivation until it encounters the complex formed by the substrate (C3b or C4b) and a cofactor protein such as factor H and complement receptor. The factor I light chain contains only the serine protease domain which is responsible for specific cleavage of C3b and C4b.

Fig.1 Overview of CFI function. (Nanthapisal, 2018)

Reference

1. Nanthapisal, S., et al. Cutaneous Vasculitis and Recurrent Infection Caused by Deficiency in Complement Factor I. Disease Frontiers in Immunology. 2018, 9: 735.