Sphingomyelin synthase related protein is a mammalian phosphatidylethanolamine phospholipase C.

Sphingomyelin synthase related protein (SMSr) has no SM synthase activity but has ceramide phosphorylethanolamine (CPE) synthase activity in vitro. Although SMSr is ubiquitously expressed in all tested tissues, the CPE levels in most mammalian tissues or cells are extremely low or undetectable. Therefore, SMSr seems not to be a functional CPE synthase in vivo and its real biological function needs to be elucidated. In this study, we utilized purified recombinant SMSr and adenovirus-mediated SMSr in vivo expression to show that SMSr has phosphatidylethanolamine phospholipases C (PE-PLC) activity, i.e., it can generate DAG through PE hydrolysis in the absence of ceramide. Further, we found that SMSr has no phosphatidylcholine (PC)-PLC, phosphatidylserine (PS)-PLC, phosphatidylglycerol (PG)-PLC, and phosphatidic phosphatase (PAP) activities, indicating that SMSr-mediated PE-PLC activity has specificity. We conclude that SMSr is a mammalian PE-PLC. Importantly, SMSr can regulate steady state levels of PE in vivo, and it should be a new tool for PE-related biological study.