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Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a zinc-dependent nucleotide phosphoesterase and member of the acid sphingomyelinase-like enzyme family.1 It is composed of an N-terminal catalytic domain and a C-terminal domain, which contains an asparagine located at position 356 (Asn356). The N-glycosylation of Asn356 is required for SMPDL3A stability, enzymatic activity, and cellular secretion.1,2 SMPDL3A is expressed in, and secreted from, osteoclasts, adipocytes, astrocytes, and macrophages and reduces local inflammation induced by nucleotide tri- or diphosphates.3,1 Its intracellular levels and secretion are increased by cAMP, cholesterol, and liver X receptor (LXR) activation, and it localizes to the lysosome, which provides the acidic environment required for its optimal catalytic activity.3,1 SMPDL3A knockout decreases cell proliferation, colony formation, and migration, as well as induces cell cycle arrest in the G0/G1 phase and apoptosis in HepG2 hepatocellular carcinoma cells.4 In vivo, SMPDL3A knockout in HepG2 cells reduces tumor volume and weight in a HepG2 xenograft mouse model. SMPDL3A levels are increased in patients with hepatocellular carcinoma (HCC) and negatively correlated with prognosis. Cayman's SMPDL3A (human, recombinant; His-tagged) protein consists of 442 amino acids and has a calculated molecular weight of 50.3 kDa. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is 51 kDa due to glycosylation.
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1. Structural basis for nucleotide hydrolysis by the acid sphingomyelinase-
2. N-
3. Sphingomyelin phosphodiesterase acid-
4. Sphingomyelin phodiesterase acid-