Cullin-4 is a member of the cullin family of related ubiquitin ligases. A pair of mammalian CUL4 proteins have been identified: CUL4A and CUL4B. The carboxy-terminal CUL4 domain interacts with Rbx1 and E2 enzymes, while the amino-terminal CUL4 domain interacts with the BPB domain of UV-damaged DNA-binding protein DDB1 to form a CUL4-DDB1 ubiquitin ligase complex. This CUL4-DDB1 complex binds a variety of WD40-containing proteins that help to enhance additional substrate recruitment. The CUL4 complex has been shown to target substrates involved in DNA repair, cell cycle progression, transcription, and development.
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