FH has 20 SCR domains, and FHR-1 has 5 of them. SCR domains of FHR-1 and FH are homologs, but FHR-1 does not possess complement regulatory domains SCR1 to 4 of FH. SCR 5 of FHR-1 is almost identical to SCR 20 of FH, except for 2 amino acids (Leu290 and Ala296 in FHR-1 instead of Ser1191 and Val1197 in FH). In some aHUS patients, these amino acids in FHR-1 are mutated back to their FH counterparts. As a result, mutant FHR-1 can bind with a higher affinity to sialic acid residues on the cell surface (eg, endothelial cells). Mutant FHR-1 molecules also bind C3 and bring it close to the cell surface, which promotes complement activation.