Sphingomyelin Phosphodiesterase 4 (SMPD4)

SMPD4 lacks an N-terminal signal peptide and contains a transmembrane region close to the C terminus, characteristic of a group of tail-anchored integral membrane proteins. Northern blot analysis detected a 4.6-kb transcript in all tissues examined, with highest levels in heart and skeletal muscle. Immunofluorescence analysis localized SMPD4 to perinuclear and diffused reticular structures in HeLa cells.SMPD4 specifically hydrolyzes sphingomyelin over other phospholipids and has a neutral pH optimum. The sphingomyelinase activity of SPMD4 was confirmed in a yeast mutant lacking endogenous sphingomyelinase. SMPD4 activity is Mg(2+)-dependent and enhanced by phosphatidylserine and inhibited by scyphostatin in a dose-dependent manner.