Complement Factor H Related Protein 2

Complement factor H (CFH), a critical regulator of the complement activity, is a large glycoprotein encode by the CFH gene. In humans, five genes (CFHR1, CFHR2, CFHR3, CFHR4, and CFHR5) are found telomerically adjacent to the CFH gene and encode five different complement factor H related (CFHR) proteins. These five CFHR proteins are divided into two major groups based on their conserved domains: Group I (CFHR1, CFHR2, and CFHR5) and Group II (CFHR3 and CFHR4).

Complement factor H-related protein 2 (CFHR2) is a plasma protein mainly produced by hepatocytes, circulating in the plasma at a concentration of 50 μg/mL. CFHR2 is composed of 4 short consensus repeat (SCR) domains, the N-terminal SCR1-SCR2, and the C-terminal SCR3-SCR4. The amino acid sequence of SCR1-2 shares almost identity to CFHR1, while SCR3-4 displays great homology to SCRs 4-5 of CFHR1 and SCRs 19-20 of CFH. CFHR2 also contains a dimerization domain at the N-terminal SCR1 that can form homo/hetero dimers with itself and CFHR1 but not with CFHR5.

It has been identified that the C-terminal of CFHR2 can bind to C3b fragment of C3 convertase, thereby interferes with the C3 cleavage by C3 convertase. But CFHR2 does not compete with CFH for C3b binding. Thus, CFHR2 inhibits the C3 convertase activity without affecting CFH function, suggesting that CFHR2 may function in concert with CFH. CFHR1 mutations associate with degeneration of macula and posterior pole and eye degenerative disease.

Fig.1 Structure diagram of CFHR1, CFHR 2, and CFHR5. (de Jorge, 2013)

Reference

1. de Jorge, E.G.; et al. Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proceedings of the National Academy of Sciences. 2013, 110(12): 4685-4690.