Function: Sphingomyelin synthases synthesize the sphingolipid, sphingomyelin, through transfer of the phosphatidyl head group, phosphatidylcholine, on to the primary hydroxyl of ceramide. The reaction is bidirectional depending on the respective levels of the sphingolipid and ceramide. Plasma membrane SMS2 can also convert phosphatidylethanolamine (PE) to ceramide phosphatidylethanolamine (CPE). Major form in liver. Required for cell growth in certain cell types. Regulator of cell surface levels of ceramide, an important mediator of signal transduction and apoptosis. Regulation of sphingomyelin (SM) levels at the cell surface affects insulin sensitivity. Ref.6 Ref.8
Catalytic activity: A ceramide + a phosphatidylcholine = a sphingomyelin + a 1,2-diacyl-sn-glycerol.
Enzyme regulation: Inhibited by bacterial PC-phospholipase C inhibitor D609. Ref.6
Subcellular location: Cell membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Note: Predominantly plasma membrane, some in Golgi apparatus. Some localization in the perinuclear region where it colocalizes with a sialyltransferase. Ref.6 Ref.9 Ref.10
Tissue specificity: Brain, heart, kidney, liver, muscle and stomach. Also expressed in a number of cell lines such as carcinoma HeLa cells, hepatoma Hep-G2 cells, and colon carcinoma Caco-2 cells. Ref.6
Post-translational modification: Palmitoylated on Cys-331, Cys-332, Cys-343 and Cys-348; which plays an important role in plasma membrane localization. Ref.10
Miscellaneous: Overexpression of the human protein in mouse causes increased non-HDL-sphingomyelin and non-HDL cholesterol levels, decreased HDL-sphingomyelin and HDL-cholesterol levels and increases lipoprotein atherogenic potential.
Sequence similarities: Belongs to the sphingomyelin synthase family.
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