Second, given that the APOBEC3C possesses a single active Z2-cytosine deaminase domain, while the APOBEC3B has double Z-coordinating (Z1 and Z2) deaminase domains [8, 41], the crystal structure determinants and functional comparison have revealed the distinct substrate preferences for binding HIV-1 DNA between the single- and double-domained APOBEC3 enzymes [42–44], raising the possibility that these two enzymes have differential DNA binding specificity which might help explain the relative differences in their observed mutagenesis in breast cancer cells, especially in the ER− cancers. The gene discussed is APOBEC3B; the disease is cancer.