Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A)

Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a secreted, N-linked glycoprotein enzyme of the metallophosphodiesterase family, closely related to human acid sphingomyelinase (aSMase) but lacking sphingomyelinase activity. Instead, SMPDL3A displays strong nucleotide phosphodiesterase activity, hydrolyzing nucleotide di- and triphosphates—including modified nucleotides such as CDP-choline, CDP-ethanolamine, and ADP-ribose—at acidic and neutral pH. The enzyme is upregulated in human macrophages by cholesterol loading, liver X receptor ligands, and cyclic AMP, potentially reducing extracellular levels of pro-inflammatory nucleotides and supporting anti-inflammatory signaling in atherosclerotic lesions. Structural studies reveal a binuclear Zn(2+)-dependent catalytic site similar to other acid sphingomyelinase family members, but with unique substrate preferences. SMPDL3A is also upregulated in certain human tumors and may serve as a functional link between lipid metabolism, nucleotide signaling, and inflammation.

Other names

Cyclic GMP-AMP phosphodiesterase SMPDL3AASML3A2',3'-cGAMP phosphodiesterase SMPDL3AASM-like phosphodiesterase 3aFLJ20177ASM3AyR36GH4.1Acid sphingomyelinase-like phosphodiesterase 3a0610010C24Rik

Catalyzes the hydrolysis of nucleotide di- and triphosphates, such as cytidine 5'-diphosphocholine (CDP-choline), cytidine diphosphate ethanolamine, and ADP-ribose, but not sphingomyelin