EGF-like domains with a C-x-D-x(4)-Y-x-C motif

Abstract

The epidermal growth factor (EGF)-like domain was first identified in pro-epidermal growth factor in 1983 and since then many proteins with EGF-like domains have been reported to be involved in pathogenesis.1,2 Pro-EGF is significantly related with oncogenesis.3,4 Mutations of EGF-like domains in fibrillin-1, low-density lipoprotein receptor (LDLR), and coagulation factor IX (FIX) are the causes of Marfan syndrome, the autosomal dominant form of familial hypercholesterolemia (FH), and hemophilia B, respectively.5–8 EGFlike domains are found in numerous secreted extracellular proteins, except for the endoplasmic transmembrane protein prostaglandin G/H synthase.9 Extracellular proteins are easily accessed by drugs and thus are good therapeutic targets, making studies of EGF-like domains medically significant.