Complement activity is non-specific and requires the assembly of regulatory molecules to tune the cascade of enzymatic cleavage events to protect bystander cells. In human, several membrane-associated proteins, complement receptor 1 (CR1), CR2, decay-accelerating factor(DAF or CD55), membrane cofactor protein (MCP or CD46) and plasma proteins, factor H and C4b-binding protein(C4bp) have been identified as complement regulators. Genes of these regulators, except for factor H, are clustered in a region which is named the regulator of complement activation (RCA) gene locus [Carroll MC et al 1988]. Analysis of the chicken genome revealed that chicken possesses an RCA gene locus similar to the human RCA [Oshiumi H et al 2005]. Three genes encoding proteins with short consensus repeats (SCRs) were identified in this region - complement regulatory secretory protein of chicken (CRES), complement regulatory protein (CREM or Cremp) and complement regulatory GPI-anchored protein (CREG). Based on the structural and functional analysis of these SRC-containing chicken proteins the authors suggested that human and chicken RCA genes evolved from a common ancestral RCA locus.
Spatial and temporal expression profiles of chicken genes involved in membrane attack complex (MAC) formation showed that a wide range of adult chicken tissues express MAC regulatory genes - CD59, vitronectin (VTN) and clusterin (CLU), with the liver being the major source of their produced transcripts. MAC regulatory chicken genes are also expressed in all the developmental stages investigated [Mikrou A and Zarkadis IK 2010]. The chicken complement regulatory proteins remain to be structurally and functionally characterized so the chicken events annotated here are mostly inferred from the human complement cascade and should be considered as a suggestive model.