Factor I Purified Human Complement Protein

Human factor I is purified from normal human serum (Fearon, D.T. (1977)). Factor I is a naturally glycosylated serine protease which cleaves and inactivates C3b and C4b. Factor I is highly specific but inactive without a cofactor such as the soluble factor H and C4b binding protein (C4BP) (Pangburn, M.K. et al (1977)). Membrane-bound cofactors include CR1 (complement receptor 1 (CD35) which is found on human red cells and other lymphoid cells) and MCP (membrane cofactor protein (CD46) which is found on most human nucleated cells). Factor I cleaves the alpha-peptide chain of C3b and C4b when these are bound to one of the cofactors. This cleavage inactivates all of the complement activating functions of these proteins producing iC3b and iC4b. Factor I can cleave the alpha chain of C3b twice and this releases a small fragment called C3f (17 amino acids, ~3 kDa). In the presence of CR1 factor can cleave iC3b releasing C3c from C3dg. C4b is cleaved rapidly at two sites separating C4c from C4d. Nomenclature for this protein has changed over time and it has been called C3b inactivator (C3b-INA), C3b/C4b inactivator, and conglutinin-activating factor (KAF).