SGMS2
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).
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.
None
The disease may be caused by variants affecting the gene represented in this entry.
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.
None
The disease may be caused by variants affecting the gene represented in this entry.
Pathway
Sphingolipid metabolism.
Post-translational modifications
Palmitoylated on Cys-331, Cys-332, Cys-343 and Cys-348; which plays an important role in plasma membrane localization.
Sequence Similarities
Belongs to the sphingomyelin synthase family.
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.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Golgi apparatus membrane
- Multi-pass membrane protein
- Primarily localized at the plasma membrane with a small fraction at the Golgi apparatus.
Alternative names
SMS2, SGMS2, Phosphatidylcholine:ceramide cholinephosphotransferase 2, Sphingomyelin synthase 2