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Literature summary extracted from

  • Traini, M.; Quinn, C.M.; Sandoval, C.; Johansson, E.; Schroder, K.; Kockx, M.; Meikle, P.J.; Jessup, W.; Kritharides, L.
    Sphingomyelin phosphodiesterase-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages (2014), J. Biol. Chem., 289, 32895-32913.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.1.4.1 gene SMPDL3A, quantitative real-time PCR expression analysis, recombinant His-tagged enzyme expression in CHO cells and secretion to the culture medium Homo sapiens
3.1.4.12 gene SMPD1, quantitative real-time PCR expression analysis, recombinant His-tagged enzyme expression in CHO cells and secretion to the culture medium Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
3.1.4.1 extracellular the enzyme is secreted Mus musculus
-
-
3.1.4.1 extracellular the enzyme is secreted, secretion of SMPDL3A is increased by cholesterol, synthetic regulated by liver X receptor ligands, and cyclic AMP in primary macrophages Homo sapiens
-
-
3.1.4.12 extracellular the enzyme is secreted Homo sapiens
-
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.1.4.1 Mg2+ activates Homo sapiens
3.1.4.1 Zn2+ activates Homo sapiens
3.1.4.12 Mg2+ activates Homo sapiens
3.1.4.12 Zn2+ activates Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.1.4.1 additional information
-
molecular mass of secreted SMPDL3A is tissue and/or species dependent Homo sapiens
3.1.4.1 additional information
-
molecular mass of secreted SMPDL3A is tissue and/or species dependent Mus musculus
3.1.4.1 45000
-
x * 52000-54000, SDS-PAGE, x * 51260, sequence calculation, x * 45000, about, deglycosylated recombinant enzyme, SDS-PAGE Homo sapiens
3.1.4.1 51260
-
x * 52000-54000, SDS-PAGE, x * 51260, sequence calculation, x * 45000, about, deglycosylated recombinant enzyme, SDS-PAGE Homo sapiens
3.1.4.1 62000
-
x * 62000, about, SDS-PAGE Mus musculus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.1.4.1 additional information Homo sapiens SMPDL3A is a functional metallophosphoesterase, and despite having no detectable activity towards sphingomyelin, possesses a nucleotide phosphodiesterase activity, particularly strongly against nucleotide triphosphates ?
-
?

Organism

EC Number Organism UniProt Comment Textmining
3.1.4.1 Homo sapiens Q92484 gene SMPDL3A
-
3.1.4.1 Mus musculus P70158 gene SMPDL3A
-
3.1.4.1 Mus musculus C57 black P70158 gene SMPDL3A
-
3.1.4.12 Homo sapiens Q8IUN0 gene SMPD1
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
3.1.4.1 glycoprotein SMPDL3A is an N-linked glycoprotein Homo sapiens
3.1.4.12 glycoprotein aSMase is an N-glycoprotein bearing 5 discrete asparagine-linked glycans with glycosylation of N395 and N520 being critical for normal secretion and function. SMPDL3A contains 7 potential N-linked glycosylation motifs (defined by the pattern NX[S|T], where X is any amino acid except proline). Notably, two of these motifs (N222 and N356) are perfectly aligned with the functionally important N395 and N520 N-linked sites of aSMase Homo sapiens

Purification (Commentary)

EC Number Purification (Comment) Organism
3.1.4.1 recombinant His-tagged enzyme from CHO cell culture medium by nickel affinity chromatography Homo sapiens
3.1.4.12 recombinant His-tagged enzyme from CHO cell culture medium by nickel affinity chromatography Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.1.4.1 blood plasma
-
Homo sapiens
-
3.1.4.1 blood plasma
-
Mus musculus
-
3.1.4.1 J-774 cell
-
Mus musculus
-
3.1.4.1 macrophage
-
Homo sapiens
-
3.1.4.1 macrophage
-
Mus musculus
-
3.1.4.1 monocyte
-
Homo sapiens
-
3.1.4.1 THP-1 cell
-
Homo sapiens
-
3.1.4.12 macrophage
-
Homo sapiens
-
3.1.4.12 monocyte
-
Homo sapiens
-
3.1.4.12 THP-1 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.4.1 4-nitrophenyl phosphocholine + H2O secreted recombinant human SMPDL3A hydrolyzes 4-nitrophenyl phosphorylcholine, a synthetic analogue of the phosphorylcholine headgroup of lipids such as sphingomyelin and phosphatidylcholine Homo sapiens 4-nitrophenol + phosphocholine
-
?
3.1.4.1 additional information SMPDL3A is a functional metallophosphoesterase, and despite having no detectable activity towards sphingomyelin, possesses a nucleotide phosphodiesterase activity, particularly strongly against nucleotide triphosphates Homo sapiens ?
-
?
3.1.4.1 additional information SMPDL3A is not an acid sphingomyelinase, but unexpectedly is active against nucleotide diphosphate and triphosphate substrates at acidic and neutral pH Homo sapiens ?
-
?
3.1.4.12 a sphingomyelin + H2O
-
Homo sapiens a ceramide + phosphocholine i.e. an N-acylsphingosine ?

Subunits

EC Number Subunits Comment Organism
3.1.4.1 ? x * 52000-54000, SDS-PAGE, x * 51260, sequence calculation, x * 45000, about, deglycosylated recombinant enzyme, SDS-PAGE Homo sapiens
3.1.4.1 ? x * 62000, about, SDS-PAGE Mus musculus

Synonyms

EC Number Synonyms Comment Organism
3.1.4.1 nucleotide phosphodiesterase
-
Homo sapiens
3.1.4.1 nucleotide phosphodiesterase
-
Mus musculus
3.1.4.1 SMPDL3A
-
Homo sapiens
3.1.4.1 SMPDL3A
-
Mus musculus
3.1.4.1 sphingomyelin phosphodiesterase, acid-like 3A
-
Homo sapiens
3.1.4.1 sphingomyelin phosphodiesterase, acid-like 3A
-
Mus musculus
3.1.4.12 acid sphingomyelinase
-
Homo sapiens
3.1.4.12 aSMase
-
Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.1.4.1 37
-
assay at Homo sapiens
3.1.4.12 37
-
assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.1.4.1 7
-
assay at Homo sapiens
3.1.4.12 5.5 7.5 assay at Homo sapiens

Expression

EC Number Organism Comment Expression
3.1.4.1 Homo sapiens the enzyme encoding gene is upregulated in bladder tumor versus healthy urothelium tissue. The enzyme is induced by cAMP, the up-regulation of enzyme secretion by raised cAMP levels are mediated by a PKA-independent pathway. The enzyme is strongly upregulated by cholesterol loading, increase in SMPDL3A mRNA expression due to cholesterol accumulation and by and synthetic LXR ligands up

General Information

EC Number General Information Comment Organism
3.1.4.1 evolution the enzyme is a member of the metallophosphoesterase enzyme family, the molecular mass of secreted SMPDL3A is tissue and/or species dependent Homo sapiens
3.1.4.1 evolution the enzyme is a member of the metallophosphoesterase enzyme family, the molecular mass of secreted SMPDL3A is tissue and/or species dependent Mus musculus
3.1.4.1 additional information expression and sequence comparisons, overview Homo sapiens
3.1.4.1 additional information expression and sequence comparisons, overview Mus musculus
3.1.4.1 physiological function SMPDL3A is the major nucleotide phosphodiesterase secreted by human THP-1 macrophages after LXR stimulation, it may play a novel role in the pathobiology of atherosclerosis. SMPDL3A is a major source of nucleotide phosphodiesterase activity secreted by LXR-stimulated human macrophages, enzyme expression and secretion is regulated by intracellular cAMP, and is regulated by liver X receptor, LXR,. The CREs in the promoter region of SMPDL3A may play a functional role in primary human macrophages. The enzyme is capable of hydrolyzing sphingomyelin in oxidized LDL particles, transforming them into a more aggregation prone form which is more readily retained by arterial proteoglycans. But SMPDL3A is not an acid sphingomyelinase, but unexpectedly is active against nucleotide diphosphate and triphosphate substrates at acidic and neutral pH Homo sapiens
3.1.4.12 evolution the enzyme is a member of the metallophosphoesterase enzyme family Homo sapiens
3.1.4.12 additional information homology model of aSMase enzyme with consensus motif NX3CX3N, where X is any amino acid, overview. The central cysteine (C385) of the motif is also involved in a disulfide bridge with C431. The enzyme aSMase contains a sphingolipid activator protein (saposin) domain in its N-terminal region followed by a proline-rich linker, this domain also plays a role in stabilizing the structure of the enzyme Homo sapiens