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Literature summary for 3.1.3.4 extracted from
- Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis (2009), J. Biol. Chem., 284, 2593-2597.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| cardiolipin | PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin | Saccharomyces cerevisiae |  |
| CDP-diacylglycerol | PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin | Saccharomyces cerevisiae | |
| phosphatidylinositol | PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin | Saccharomyces cerevisiae | |
| Triton X-100 | activates by forming a mixed micelle with the lipid substrate PA, providing a membrane mimic for catalysis | Saccharomyces cerevisiae | |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expression of lipins 1-3 in HEK-293 cells | Mus musculus |
| gene PAH1, expression in Escherichia coli | Saccharomyces cerevisiae |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| D398E | catalytically inactive PAP enzymes with a mutation in a conserved NLIP domain residue fail to complement phenotypes caused by the pah1DELTA mutation | Mus musculus |
| D400E | catalytically inactive PAP enzymes with a mutation in a conserved NLIP domain residue fail to complement phenotypes caused by the pah1DELTA mutation | Mus musculus |
| G80R | catalytically inactive PAP enzymes with a mutation in a conserved NLIP domain residue fail to complement phenotypes caused by the pah1DELTA mutation | Mus musculus |
| additional information | gene Lpin1 is the mutated gene in the fatty liver dystrophy, fld, in mouse. The phenotypes associated with the pah1DELTA mutation, which also include slow growth, temperature sensitivity, and respiratory deficiency are specifically due to the loss of PAP activity. In addition, mice lacking lipin 1 exhibit peripheral neuropathy that is characterized by myelin degradation, Schwann cell dedifferentiation and proliferation, and a reduction in nerve conduction velocity, These effects are mediated through the MEK/ERK pathway that is activated by elevated levels of PA due to the loss of PAP activity | Mus musculus |
| additional information | generation of a pah1DELTA mutant, phenotype, overview | Saccharomyces cerevisiae |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| ATP | the mechanism of inhibition by ATP is complex, affecting both the Vmax and Km for phosphatidic acid, competitive to Mg2+ and involving the chelation of the cofactor | Saccharomyces cerevisiae | |
| CTP | the mechanism of inhibition by CTP is complex, affecting both the Vmax and Km for phosphatidic acid, competitive to Mg2+ and involving the chelation of the cofactor | Saccharomyces cerevisiae | |
| phytosphingosine | inhibition of PAH1 | Saccharomyces cerevisiae | |
| sphinganine | inhibition of PAH1 | Saccharomyces cerevisiae | |
| sphingosine | inhibition of PAH1 | Saccharomyces cerevisiae | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | mainly | Saccharomyces cerevisiae | 5829 | - |
| cytosol | the phosphorylated forms of lipins 1 and 2 in HeLa cells and adipocytes are enriched in the cytosolic fraction, whereas the dephosphorylated forms are enriched in the membrane fraction | Homo sapiens | 5829 | - |
| membrane | association | Saccharomyces cerevisiae | 16020 | - |
| membrane | the phosphorylated forms of lipins 1 and 2 in HeLa cells and adipocytes are enriched in the cytosolic fraction, whereas the dephosphorylated forms are enriched in the membrane fraction | Homo sapiens | 16020 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | dependent on | Saccharomyces cerevisiae | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 95000 | - |
1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE | Saccharomyces cerevisiae |
| 124000 | - |
1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE | Saccharomyces cerevisiae |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| a 3-sn-phosphatidate + H2O | Mus musculus | key enzyme in the regulation of lipid synthesis, it PAP generates a pool of diacylglycerol used for protein kinase C activation, and attenuates the signaling functions of phosphatidic acid | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
| a 3-sn-phosphatidate + H2O | Saccharomyces cerevisiae | key enzyme in the regulation of lipid synthesis, it PAP generates a pool of diacylglycerol used for protein kinase C activation, and attenuates the signaling functions of phosphatidic acid | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
| a 3-sn-phosphatidate + H2O | Homo sapiens | key enzyme in the regulation of lipid synthesis, PAP generates a pool of diacylglycerol used for protein kinase C activation, and attenuates the signaling functions of phosphatidic acid | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
genes Lpin1, Lpin2, and Lpin3 | - |
| Mus musculus | - |
genes Lpin1, Lpin2, and Lpin3 | - |
| Saccharomyces cerevisiae | - |
gene PAH1, formerly SMP2 | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | PAP PAH1 is a target for multiplec protein kinases, including cyclin-dependent kinase Cdk1, Pho85, and Dbf2-Mob1. PAP is phosphorylated by Cdk1 in a cell cycle-dependent manner, a purified phosphorylation-deficient Ser/Thr 3 Ala septuple mutant enzyme exhibits elevated PAP activity | Saccharomyces cerevisiae |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| a 3-sn-phosphatidate + H2O | - |
Mus musculus | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
| a 3-sn-phosphatidate + H2O | - |
Homo sapiens | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
| a 3-sn-phosphatidate + H2O | - |
Saccharomyces cerevisiae | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
| a 3-sn-phosphatidate + H2O | key enzyme in the regulation of lipid synthesis, it PAP generates a pool of diacylglycerol used for protein kinase C activation, and attenuates the signaling functions of phosphatidic acid | Mus musculus | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
| a 3-sn-phosphatidate + H2O | key enzyme in the regulation of lipid synthesis, it PAP generates a pool of diacylglycerol used for protein kinase C activation, and attenuates the signaling functions of phosphatidic acid | Saccharomyces cerevisiae | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
| a 3-sn-phosphatidate + H2O | key enzyme in the regulation of lipid synthesis, PAP generates a pool of diacylglycerol used for protein kinase C activation, and attenuates the signaling functions of phosphatidic acid | Homo sapiens | a 1,2-diacyl-sn-glycerol + phosphate | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| monomer | 1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE | Saccharomyces cerevisiae |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| 3-sn-phosphatidate phosphohydrolase | - |
Mus musculus |
| 3-sn-phosphatidate phosphohydrolase | - |
Homo sapiens |
| 3-sn-phosphatidate phosphohydrolase | - |
Saccharomyces cerevisiae |
| lipin | - |
Mus musculus |
| lipin | - |
Homo sapiens |
| PA phosphatase | - |
Mus musculus |
| PA phosphatase | - |
Homo sapiens |
| PA phosphatase | - |
Saccharomyces cerevisiae |
| PAP | - |
Mus musculus |
| PAP | - |
Homo sapiens |
| PAP | - |
Saccharomyces cerevisiae |
| phosphatidic acid phosphatase | - |
Mus musculus |
| phosphatidic acid phosphatase | - |
Homo sapiens |
| phosphatidic acid phosphatase | - |
Saccharomyces cerevisiae |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7 | 7.5 | - |
Saccharomyces cerevisiae |
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