Regulators of Complement Activation (RCA) Gene Cluster

Regulator of Complement Activation / RCA Gene Cluster Background

The complement system is a potent recognition and effector pathway that plays a major role in the immune response. It mediates the destruction and disposal of immune complexes and foreign substances through interactions between complement proteolytic fragments deposited on targets and complement receptors on cell surfaces. To faciliate this process, and to prevent damage to self-tissue, a remarkable family of control proteins (the regulators of complement activation or RCA proteins) has evolved. Each member interacts with a derivative of C4 and/or C3, shares a repeating polypeptide motif, and is encoded at a single genetic region, the RCA cluster.

Regulator of Complement Activation / RCA Gene Locus

It is generally accepted that the C susceptibility in host cells is regulated mainly at C3 step. In humans, the complement regulatory proteins consist of tandemly arranged domains named short consensus repeats (SCRs) and their genes cluster in a region designated as the regulator of complement activation (RCA) locus. Each SCR consists of 60–70 aa, including 4 highly conserved cysteines. The cysteines form disulfide bonds, folding the SCRs into a rigid triple-loop structure. Although the proteins in the RCA family vary in size, they share significantly similar in three-dimensional structures due to conserved amino acids at specific locations. Considering their similarities and configurations, RCA locus might have been expanding by repeating gene duplications.

In humans, two soluble forms, factor H and C4b-binding protein (C4bp), and four membrane forms, CR1 (CD35), CR2 (CD21), decay-accelerating factor (DAF) (CD55), and membrane cofactor protein (MCP) (CD46), have been identified as complement regulatory proteins. Genes for all these regulators, except for factor H, were mapped to the RCA locus, 1q32. This locus is in close proximity to the 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) gene in mammals. Factor H gene is also mapped to the long arm of chromosome 1 but outside of the RCA locus.

Regulator of Complement Activation / RCA Gene Cluster (Proteins | Antibodies | Genes | ELISA Kits)

Regulator of Complement Activation / RCA Gene Cluster References

1. Hourcade D, et al. (1989). The regulators of complement activation (RCA) gene cluster. Advances in immunology, 45, 381-416.
2. Oshiumi H, et al. (2005). Regulator of complement activation (RCA) locus in chicken: identification of chicken RCA gene cluster and functional RCA proteins. The Journal of Immunology, 175(3), 1724-1734.