Cerebral Cavernous Malformation 2 (CCM2)

CCM2 encodes a scaffold protein that functions in the stress-activated p38 Mitogen-activated protein kinase (MAPK) signaling cascade. The protein interacts with SMAD specific E3 ubiquitin protein ligase 1 (also known as SMURF1) via a phosphotyrosine binding domain to promote RhoA degradation. The protein is required for normal cytoskeletal structure, cell-cell interactions, and lumen formation in endothelial cells. Mutations in this gene result in cerebral cavernous malformations. Multiple transcript variants encoding different isoforms have been found for this gene. The gene was chosen because its translation product contains a putative PTP domain. The same domain had been found in ICAP1-alpha, a binding partner of the CCM1 product KRIT1, which is mutant in cerebral cavernous malformations type 1.