Thalidomide-binding C-terminal domain of cereblon (CRBN) and similar protein domains
Cereblon is part of an E3 ubiquitin ligase complex, together with damaged DNA-binding protein 1 (DDB1), CUL4A and ROC1. Cereblon interacts directly with DDB1, although the C-terminal domain characterized here does not contribute to that interaction. Ubiquination of cellular targets by this complex increases levels of FGF8 and FGF10, which was shown to affect the development of limbs and auditory vesicles in embryogenesis. The C-terminal domain of Cereblon was shown to contain the binding site for thalidomide and its analogs, a class of teratogenic drugs that exhibit an antiproliferative effect on myelomas. Mutations in CRBN, some of which map onto the C-terminal domain, were associated with autosomal recessive mental retardation, which may have to do with interactions between CRBN and ion channels in the brain.
Jiyao W et al.(2023). "The conserved domain database in 2023.",