Cullin E3 ligase protein family in human cells. (A). Diagram of human Cullin 1, Cullin 2, Cullin 3, Cullin 4A, Cullin 4B, Cullin 5, and Cullin 7. The cullin domain of these proteins is shown. Numbers represent the amino acid number. (B). The modularity of Cullin 4A E3 ligase. Cullin 4A interacts with the Ring finger-containing protein ROC1 through its C-terminus Cullin domain. The N-terminus of Cullin 4A recruits substrates through DDB1-interacting proteins to ROC1, which interacts with ubiquitin conjugating enzymes (Ubc5) and mediates the ubiquitylation reaction.