CDH1 and famililal cerebral cavernous malformations: Disruption of the SMURF1 homodimer is achieved by allosteric interactions of several adaptor proteins including CKIP (casein kinase-interacting protein), which binds to the WW domain [106]; CDH1 (Cadherin 1), which binds to the C2 domain [104]; or CCM2 (cerebral cavernous malformations 2), which binds to the HECT domain (Fig. 7a) [107].