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Literature summary for 3.1.4.1 extracted from
- Sphingomyelin phosphodiesterase-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages (2014), J. Biol. Chem., 289, 32895-32913.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene SMPDL3A, quantitative real-time PCR expression analysis, recombinant His-tagged enzyme expression in CHO cells and secretion to the culture medium | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| extracellular | the enzyme is secreted | Mus musculus | - |
- |
| 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 | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | activates | Homo sapiens |  |
| Zn2+ | activates | Homo sapiens | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| additional information | - |
molecular mass of secreted SMPDL3A is tissue and/or species dependent | Homo sapiens |
| additional information | - |
molecular mass of secreted SMPDL3A is tissue and/or species dependent | Mus musculus |
| 45000 | - |
x * 52000-54000, SDS-PAGE, x * 51260, sequence calculation, x * 45000, about, deglycosylated recombinant enzyme, SDS-PAGE | Homo sapiens |
| 51260 | - |
x * 52000-54000, SDS-PAGE, x * 51260, sequence calculation, x * 45000, about, deglycosylated recombinant enzyme, SDS-PAGE | Homo sapiens |
| 62000 | - |
x * 62000, about, SDS-PAGE | Mus musculus |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q92484 | gene SMPDL3A | - |
| Mus musculus | P70158 | gene SMPDL3A | - |
| Mus musculus C57 black | P70158 | gene SMPDL3A | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| glycoprotein | SMPDL3A is an N-linked glycoprotein | Homo sapiens |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His-tagged enzyme from CHO cell culture medium by nickel affinity chromatography | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| blood plasma | - |
Homo sapiens | - |
| blood plasma | - |
Mus musculus | - |
| J-774 cell | - |
Mus musculus | - |
| macrophage | - |
Homo sapiens | - |
| macrophage | - |
Mus musculus | - |
| monocyte | - |
Homo sapiens | - |
| THP-1 cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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 | - |
? | |
| 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 | ? | - |
? | |
| 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 | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 52000-54000, SDS-PAGE, x * 51260, sequence calculation, x * 45000, about, deglycosylated recombinant enzyme, SDS-PAGE | Homo sapiens |
| ? | x * 62000, about, SDS-PAGE | Mus musculus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| nucleotide phosphodiesterase | - |
Homo sapiens |
| nucleotide phosphodiesterase | - |
Mus musculus |
| SMPDL3A | - |
Homo sapiens |
| SMPDL3A | - |
Mus musculus |
| sphingomyelin phosphodiesterase, acid-like 3A | - |
Homo sapiens |
| sphingomyelin phosphodiesterase, acid-like 3A | - |
Mus musculus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7 | - |
assay at | Homo sapiens |
Expression
| Organism | Comment | Expression |
|---|---|---|
| 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
| General Information | Comment | Organism |
|---|---|---|
| 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 |
| 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 |
| additional information | expression and sequence comparisons, overview | Homo sapiens |
| additional information | expression and sequence comparisons, overview | Mus musculus |
| 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 |
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