LMPD Database

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LMP002819

UniProt Annotations

Entry Information
Gene Namesphingomyelin synthase 2
Protein EntryQ9D4B1_MOUSE
UniProt IDQ9D4B1
SpeciesMouse
Comments
Comment typeDescription
Catalytic ActivityA ceramide + a phosphatidylcholine = a sphingomyelin + a 1,2-diacyl-sn-glycerol.
Disruption PhenotypeNull mice are viable but exhibit increased cell membrane ceramide and decreased sphingomyelin levels. In both skeletal muscle and adipose tissue, there is a significant increase in glucose update. This leads to increased insulin sensitivity and ameliorated high-fat diet-induced obesity. There is blunted NFKB1- and MAP kinase-mediated responses to inflammatory stimuli and macrophages display increased cholesterol efflux into blood circulation. Liver SMS activity is dramatically reduced (by about 80%) but only small change in macrophage SMS2 activity (16%). No change in glycosphingolipid levels in plasma. Atherosclerosis in SMS2(-/-)/LDLR(-/-) mice is significantly decreased. {ECO:0000269|PubMed:19590047, ECO:0000269|PubMed:21844222, ECO:0000269|PubMed:22580896}.
FunctionSphingomyelin 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. {ECO:0000269|PubMed:19590047, ECO:0000269|PubMed:21844222, ECO:0000269|PubMed:22580896, ECO:0000269|PubMed:22849442}.
PtmPalmitoylated on Cys-331, Cys-332, Cys-343 and Cys-348; which plays an important role in plasma membrane localization.
SimilarityBelongs to the sphingomyelin synthase family.
Subcellular LocationCell membrane ; Multi-pass membrane protein . Golgi apparatus membrane {ECO:0000250}; Multi-pass membrane protein . Note=Predominantly plasma membrane, some in Golgi apparatus.
Tissue SpecificityExpressed in liver and macrophages.