The complement component proteins C3, C4 and C5 are potent anaphylatoxins that are released during complement activation, a system of ligand-surface protein interactions specific to cells of hematopoietic lineage. These proteins belong to the α2-macroglobulin family, but retain distinctive features including an anaphylatoxin domain and a netrin (NTR) domain. The human C4 gene is polymorphic at two loci, C4A and C4B, mapping to chromosome 6p21.32. C4A expresses the Rodgers (Rg) blood group Ag, while C4B expresses the Chido (Ch) blood group Ag. C4 is expressed as a precursor that is cleaved into α, β and γ chains, all of which are non-identical cleavage products. The α chain of C4 may be cleaved to produce an acidic isotype, C4a, which reacts with amino groups, and a basic isotype, C4b, which reacts with hydroxyl groups. Deficiency in the C4 gene is associated with autoimmune or immune complex disorders, such as systemic lupus erythematosus.
