Complement Factor H Related Protein 5

CFHR5, also known as complement factor H-related protein 5 or FHR-5, is a 65 kDa protein that is encoded by the CFHR5 gene. It belongs to the factor H-related protein family which consists of the complement and immune regulators factor H, the factor H-like protein 1 (FHL-1), and five factor H-related proteins. Members of this family are exclusively composed of individually folded protein domains called short consensus repeats (SCRs) or complement control modules. The CFHR5 protein consists of 9 SCRs, with the first two repeats having heparin-binding properties, a region within repeats 5-7 possessing texing heparin-binding and C reactive protein (CRP)-binding characteristics, and the C-terminal repeats similar to a complement component 3 b (C3b)-binding domain. This protein acts as a complement activator and plays an important role in the regulation of the alternative complement pathway. It is co-localized with complement C3, binds C3b in a dose-dependent way, and is recruited to tissues damaged by C-reactive protein. CFHR5 also can suppress the C3 convertase and serve as a co-factor for the cleavage of C3b.

The deficiency of CFHR5 is associated with several kidney diseases such as CFHR5 nephropathy. Mutations with loss of function in CFHR5 were detected in patients with the disease CFHR5 nephropathy, which indicates CFHR5 is important in protecting the kidneys from attack by the complement system.

Fig. 1 CFHR5 belongs to the human factor H protein family.¹

Reference

1. Józsi, Mihály. "Factor H family proteins in complement evasion of microorganisms." Frontiers in immunology 8 (2017): 571