CFHR1

Background

In the complement factor H family, there are five CFHR proteins have been identified, which are divided into two major groups, Group I and Group II, based on their conserved domains. Complement factor H-related protein 1 (CFHR1), a member of Group I CFHR proteins, is a plasma protein circulating in two glycosylated forms at the concentration of 70 to 100 μg/mL. CFHR1 is composed of five short consensus repeat (SCR) domains or complement control protein (CCP) domains. The N-terminal two SCRs, SCR1 and SCR2, exhibit sequence homology to SCR6 and SCR7 of CFH, and share high amino acid identity to SCR1 and SCR2 of CFHR2 and CFHR5. CFHR1 has a dimerization domain at the N-terminus that can form heterodimers with CFHR2 and CFHR5. The sequence of C-terminal SCR3, SCR4, and SCR5 are almost identical to the SCR18-20 of CFH, except for two amino acid differences.

CFHR1 mutations or deficiency are closely related to Hemolytic Uremic Syndrome Atypical 1 and Macular Degeneration Age-Related 1 since CFHR1 is a regulator for complement alternative pathway. However, CFHR1 functions in a manner different from CFH.

1. CFHR1 (SCR1 and SCR2) inhibits C5 cleavage by binding to C3b of the C5 convertase of the complement alternative pathway, not C3 convertase. Thus, the formation of anaphylactic C5a generation and cytolytic membrane attack complex (MAC) are blocked.
2. CFHR1 also inhibits the assembly of the C5bC6 complex, an intermediate product of MAC.
3. The C-terminal SCR3-5 can bind to C3b, C3d, and heparin on the host surface, competing with the binding of complement factor B to C3b thereby inhibiting the complement alternative pathway amplification.

Fig.1 Structure of CFHR1.^1,3

CFHR1 Functional Service

Creative Biolabs provides a comprehensive range of CFHR1-related products, encompassing anti-CFHR1 monoclonal/polyclonal Antibodies, CFHR1 ELISA Assay Kits, recombinant CFHR1 Proteins, and CFHR1 blocking Peptides, aiding to study CFHR1 expression, function, and interactions in various cellular and disease contexts.

Fig.2 CFHR1 blocks other CFH-interaction sites on C3b.^2,3

CFHR1 functional testing is essential for the role of CFHR1 in immune regulation, complement system modulation, and inflammatory diseases, providing valuable insights into its potential as a biomarker or therapeutic target. Our testing methods, including ELISA, recombinant protein assays, and blocking peptide studies, allow for the quantification and functional assessment of CFHR1 activity. Research has demonstrated that CFHR1 acts as a regulator of complement factor H, and its dysfunction can lead to dysregulation of the complement system. Functional assays of CFHR1 have shown that CFHR1 deficiency or mutations contribute to the development of age-related macular degeneration, with elevated CFHR1 levels being associated with immune-mediated diseases.

Creative Biolabs provides CFHR1-functional services, including functional assays, biomarker validation, etc. We help customers design and execute experiments to answer their specific research questions, providing expert guidance and technical support throughout the process. With the latest technology and professional expertise, we ensure reliable and high-quality functional testing for CFHR1.

References

1. Zipfel, Peter F., et al. "Deletion of complement factor H–related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome." PLoS genetics 3.3 (2007): e41.
2. Hannan, Jonathan P., et al. "Mapping the complement factor H-related protein 1 (CFHR1): C3b/C3d interactions." PloS one 11.11 (2016): e0166200.
3. Distributed under Open Access license CC BY 4.0, without modification.