CCM2-like scaffold protein (CCM2L)

CCM2-like scaffold protein (CCM2L) is a paralog of the CCM2 (cerebral cavernous malformation 2) protein and shares substantial sequence homology and domain structure, including a phosphotyrosine-binding (PTB) domain and a C-terminal harmonin-homology domain[2][5]. Like CCM2, CCM2L acts as a scaffolding or adaptor protein but lacks enzymatic activity. It has been shown to bind KRIT1 (CCM1) via its PTB domain and MEKK3 via its C-terminal region, thereby modulating MEKK3 kinase activity and downstream MAP kinase signaling[2][5][7]. CCM2L displays primarily endothelial-specific expression and differs from CCM2 in its regulation; for example, its expression in endothelial cells is modulated by cell density, shear flow, and statins, suggesting a role in vascular adaptation to environmental cues[5]. Functionally, CCM2L helps regulate angiogenesis and cardiovascular development, coordinating endothelial cell signaling, and vascular stability. Animal studies show that loss of CCM2L leads to impaired circulation, heart enlargement, and defective vascular development, highlighting its physiological importance[2][5]. The dysfunction of CCM2L, together with CCM2, is linked to the pathogenesis of cerebral cavernous malformations, a disease characterized by abnormal blood vessel formation in the brain[2][5][7]. CCM2L is neither a classical drug target nor an enzyme but is best categorized as a cellular signaling scaffold protein whose disruption may contribute to vascular disease.

Other names

Cerebral cavernous malformations 2 protein-likeCCM2LC20orf160CCM2-likedJ310O13.5cerebral cavernous malformation 2-like