SMPDL3A
Function
Cyclic-nucleotide phosphodiesterase that acts as a negative regulator of innate immunity by mediating degradation of 2',3'-cGAMP, thereby inhibiting the cGAS-STING signaling (PubMed:37890481). Specifically linearizes 2',3'-cGAMP into 2'5'-bond pGpA and further hydrolyzes pGpA to produce GpA (PubMed:37890481). Also has in vitro nucleotide phosphodiesterase activity with nucleoside triphosphates, such as ATP (PubMed:25288789, PubMed:26783088). Has in vitro activity with p-nitrophenyl-TMP (PubMed:25288789). Has lower activity with nucleoside diphosphates, and no activity with nucleoside monophosphates (PubMed:25288789, PubMed:26783088, PubMed:28104755). Has in vitro activity with CDP-choline, giving rise to CMP and phosphocholine. Has in vitro activity with CDP-ethanolamine (PubMed:26783088). Does not have sphingomyelin phosphodiesterase activity (PubMed:25288789, PubMed:26783088).
Post-translational modifications
N-glycosylation is required for protein maturation, secretion and phosphodiesterase activity.
Sequence Similarities
Belongs to the acid sphingomyelinase family.
Tissue Specificity
Detected in blood serum. Detected in macrophages (at protein level).
Cellular localization
- Secreted
Alternative names
ASML3A, SMPDL3A, Cyclic GMP-AMP phosphodiesterase SMPDL3A, Acid sphingomyelinase-like phosphodiesterase 3a, ASM-like phosphodiesterase 3a