Collagen and calcium-binding EGF domain-containing protein 1 (CCBE1)

Collagen and calcium-binding EGF domain-containing protein 1 (CCBE1) is a secreted extracellular matrix protein essential for the development of the lymphatic system and the heart, particularly for the proper formation of lymphatic vessels and coronary vessels[1][2][4]. CCBE1 is characterized by two EGF-like domains (including a calcium-binding EGF domain) at the N-terminus and two collagen-like repeats at the C-terminus; the protein undergoes chondroitin sulfate and glycosylation modifications[2][4][5]. It facilitates the maturation, migration, and differentiation of lymphangioblasts—immature cells which become the lining of lymphatic vessels[1][2][4][6]. In lymphangiogenesis, CCBE1 is a critical co-factor facilitating proteolytic activation of vascular endothelial growth factor-C (VEGF-C), enhancing its binding to VEGFR-3 and driving the formation of lymphatic vasculature[2][3][4][5]. Mutations in the CCBE1 gene cause Hennekam syndrome, a rare disorder characterized by malformation of lymphatic vessels, primary lymphedema, lymphangiectasia, and a variety of cardiac defects[1][2][4][6]. Recent studies also implicate CCBE1 as a regulator of heart development, impacting progenitor cell populations and epicardial-derived coronary vessels[2][4]. Dysregulation or mutation of CCBE1 has been implicated in several cancers, likely related to abnormal lymphangiogenesis and tumor metastasis[2][4]. There are currently no drugs known to interact directly with CCBE1, and the protein is not widely targeted therapeutically, though it is of ongoing research interest for its role in lymphatic and cardiac disorders.

Other names

FLJ30681full of fluid protein homologKIAA1983UNQ1921/PRO4395HKLLS1Collagen and calcium binding EGF domains 1Full of fluid protein homologCollagen and calcium-binding EGF domain-containing protein 1