Alternative titles; symbols
HGNC Approved Gene Symbol: SMPDL3A
Cytogenetic location: 6q22.31 Genomic coordinates (GRCh38) : 6:122,789,258-122,809,720 (from NCBI)
Using yeast 2-hybrid analysis with the sequence of the DBCCR1 gene (602865) as query to screen a human bladder cDNA library, Wright et al. (2002) identified SMPDL3A. The 454-amino acid protein has a predicted molecular mass of 51.2 kD.
Traini et al. (2014) reported that SMPDL3A protein has an N-terminal signal sequence, classical phosphodiesterase consensus motifs, 5 predicted metal-binding residues, and 7 potential N-glycosylation sites. Western blot analysis of human monocyte-derived macrophages detected a doublet of SMPDL3A at apparent molecular masses of approximately 52 and 54 kD. Circulating SMPDL3A was also detected in normal human and mouse serum. Glycosidase treatment reduced the apparent molecular mass of SMPDL3A, revealing that it is a glycoprotein. Immunofluorescence analysis of transfected Chinese hamster ovary cells detected human SMPDL3A in a punctate cytoplasmic distribution, with highest concentration in the perinuclear region.
By Northern and Western blot analysis, Wright et al. (2002) showed that transient transfection of SMPDL3A and DBCCR1 in bladder tumor cells resulted in overexpression of DBCCR1 and upregulation of SMPDL3A mRNA and protein. Only full-length DBCCR1 increased SMPDL3A expression, suggesting that the membrane attack complex/perforin domain of the N terminus of DBCCR1 is not sufficient for SMPDL3A interaction. Wright et al. (2002) found that SMPDL3A expression was increased in 8 of 12 bladder tumor specimens and only detectable in 1 corresponding normal urothelium specimen.
Using microarray analysis, Traini et al. (2014) found that expression and secretion of SMPDL3A were upregulated by cholesterol loading in primary human macrophages. SMPDL3A expression and secretion were also upregulated by activation of liver X receptor (see 602423) and by cyclic AMP. Using a panel of synthetic substrates, Traini et al. (2014) showed that SMPDL3A had phosphodiesterase and nucleotide phosphoesterase activities. Optimal activity was observed in pH range 4.0 to 6.0, with activity significantly reduced at pH above 7. Activity was moderately stimulated by Ca(2+) or Mg(2+) and strongly inhibited by Zn(2+). The nucleotide phosphoesterase activity of SMPDL3A was high with nucleotide triphosphates and lower with nucleotide diphosphates. SMPDL3A had no activity against nucleotide monophosphates, cyclic nucleotide phosphates, or any phosphorylcholine-containing lipid examined, including sphingomyelin.
The International Radiation Hybrid Mapping Consortium mapped the SMPDL3A gene to chromosome 6 (RH70964).
Hartz (2014) mapped the SMPDL3A gene to chromosome 6q22.31 based on an alignment of the SMPDL3A sequence (GenBank AK000184) with the genomic sequence (GRCh38).
Hartz, P. A. Personal Communication. Baltimore, Md. 11/26/2014.
Traini, M., Quinn, C. M., Sandoval, C., Johansson, E., Schroder, K., Kockx, M., Meikle, P. J., Jessup, W., Kritharides, L. Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages. J. Biol. Chem. 289: 32895-32913, 2014. [PubMed: 25288789] [Full Text: https://doi.org/10.1074/jbc.M114.612341]
Wright, K. O., Messing, E. M., Reeder, J. E. Increased expression of the acid sphingomyelinase-like protein ASML3a in bladder tumors. J. Urol. 168: 2645-2649, 2002. [PubMed: 12442002] [Full Text: https://doi.org/10.1016/S0022-5347(05)64236-X]