SGMS2

Sphingomyelin, a major component of cell and Golgi membranes, is made by the transfer of phosphocholine from phosphatidylcholine onto ceramide, with diacylglycerol as a side product. The protein encoded by this gene is an enzyme that catalyzes this reaction primarily at the cell membrane. The synthesis is reversible, and this enzyme can catalyze the reaction in either direction. The encoded protein is required for cell growth. Three transcript variants encoding the same protein have been found for this gene. There is evidence for more variants, but the full-length nature of their transcripts has not been determined.

Full Name

Sphingomyelin Synthase 2

Function

Sphingomyelin synthase that primarily contributes to sphingomyelin synthesis and homeostasis at the plasma membrane. Catalyzes the reversible transfer of phosphocholine moiety in sphingomyelin biosynthesis: in the forward reaction transfers phosphocholine head group of phosphatidylcholine (PC) on to ceramide (CER) to form ceramide phosphocholine (sphingomyelin, SM) and diacylglycerol (DAG) as by-product, and in the reverse reaction transfers phosphocholine from SM to DAG to form PC and CER. The direction of the reaction appears to depend on the levels of CER and DAG in the plasma membrane (PubMed:14685263, PubMed:17449912, PubMed:17982138, PubMed:18370930).
Does not use free phosphorylcholine or CDP-choline as donors (PubMed:14685263).
Can also transfer phosphoethanolamine head group of phosphatidylethanolamine (PE) on to ceramide (CER) to form ceramide phosphoethanolamine (CPE) (PubMed:19454763).
Regulates receptor-mediated signal transduction via mitogenic DAG and proapoptotic CER, as well as via SM, a structural component of membrane rafts that serve as platforms for signal transduction and protein sorting (PubMed:17449912, PubMed:17982138).
To a lesser extent, plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1 (PubMed:18370930, PubMed:21980337).
Required for normal bone matrix mineralization (PubMed:30779713).

Biological Process

Biological Process ceramide biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process phosphorylationIEA:UniProtKB-KW
Biological Process regulation of bone mineralizationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process sphingolipid biosynthetic processTAS:Reactome
Biological Process sphingomyelin biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cell membrane
Golgi apparatus membrane
Primarily localized at the plasma membrane with a small fraction at the Golgi apparatus.

Involvement in disease

Calvarial doughnut lesions with bone fragility (CDL):
A rare autosomal dominant bone disease characterized by low bone density, distinctive X-ray translucencies of the skull, multiple fractures, elevated serum alkaline phosphatase, and dental caries. Patients present with childhood onset of primary osteoporosis and typical sclerotic doughnut-shaped lesions in the cranial bones.
Calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia (CDLSMD):
A severe form of calvarial doughnut lesions with bone fragility, a rare autosomal dominant disease characterized by low bone density, distinctive X-ray translucencies of the skull, multiple fractures, elevated serum alkaline phosphatase, and dental caries. CDLSMD patients show neonatal onset of fractures, severe short stature, marked cranial sclerosis, and spondylometaphyseal dysplasia.

PTM

Palmitoylated on Cys-331, Cys-332, Cys-343 and Cys-348; which plays an important role in plasma membrane localization.