BRENDA - Enzyme Database

Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis

Carman, G.M.; Han, G.; J. Biol. Chem. 284, 2593-2597 (2009)

Data extracted from this reference:

Activating Compound
EC Number
Activating Compound
Commentary
Organism
Structure
3.1.3.4
cardiolipin
PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin
Saccharomyces cerevisiae
3.1.3.4
CDP-diacylglycerol
PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin
Saccharomyces cerevisiae
3.1.3.4
phosphatidylinositol
PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin
Saccharomyces cerevisiae
3.1.3.4
Triton X-100
activates by forming a mixed micelle with the lipid substrate PA, providing a membrane mimic for catalysis
Saccharomyces cerevisiae
Cloned(Commentary)
EC Number
Commentary
Organism
3.1.3.4
expression of lipins 1-3 in HEK-293 cells
Mus musculus
3.1.3.4
gene PAH1, expression in Escherichia coli
Saccharomyces cerevisiae
Engineering
EC Number
Amino acid exchange
Commentary
Organism
3.1.3.4
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
3.1.3.4
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
3.1.3.4
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
3.1.3.4
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
3.1.3.4
additional information
generation of a pah1DELTA mutant, phenotype, overview
Saccharomyces cerevisiae
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.3.4
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
3.1.3.4
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
3.1.3.4
phytosphingosine
inhibition of PAH1
Saccharomyces cerevisiae
3.1.3.4
sphinganine
inhibition of PAH1
Saccharomyces cerevisiae
3.1.3.4
sphingosine
inhibition of PAH1
Saccharomyces cerevisiae
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
3.1.3.4
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
-
3.1.3.4
cytosol
mainly
Saccharomyces cerevisiae
5829
-
3.1.3.4
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
-
3.1.3.4
membrane
association
Saccharomyces cerevisiae
16020
-
Metals/Ions
EC Number
Metals/Ions
Commentary
Organism
Structure
3.1.3.4
Mg2+
dependent on
Saccharomyces cerevisiae
Molecular Weight [Da]
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
3.1.3.4
95000
-
1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE
Saccharomyces cerevisiae
3.1.3.4
124000
-
1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE
Saccharomyces cerevisiae
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
3.1.3.4
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
-
-
?
3.1.3.4
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
-
-
?
3.1.3.4
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
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.1.3.4
Homo sapiens
-
genes Lpin1, Lpin2, and Lpin3
-
3.1.3.4
Mus musculus
-
genes Lpin1, Lpin2, and Lpin3
-
3.1.3.4
Saccharomyces cerevisiae
-
gene PAH1, formerly SMP2
-
Posttranslational Modification
EC Number
Posttranslational Modification
Commentary
Organism
3.1.3.4
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)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.1.3.4
a 3-sn-phosphatidate + H2O
-
693238
Mus musculus
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
a 3-sn-phosphatidate + H2O
-
693238
Homo sapiens
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
a 3-sn-phosphatidate + H2O
-
693238
Saccharomyces cerevisiae
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
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
693238
Mus musculus
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
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
693238
Saccharomyces cerevisiae
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
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
693238
Homo sapiens
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
Subunits
EC Number
Subunits
Commentary
Organism
3.1.3.4
monomer
1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE
Saccharomyces cerevisiae
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
3.1.3.4
7
7.5
-
Saccharomyces cerevisiae
Activating Compound (protein specific)
EC Number
Activating Compound
Commentary
Organism
Structure
3.1.3.4
cardiolipin
PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin
Saccharomyces cerevisiae
3.1.3.4
CDP-diacylglycerol
PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin
Saccharomyces cerevisiae
3.1.3.4
phosphatidylinositol
PAH1-encoded PAP activity is enhanced by the phospholipids CDP-diacylglycerol, phosphatidylinositol, and cardiolipin
Saccharomyces cerevisiae
3.1.3.4
Triton X-100
activates by forming a mixed micelle with the lipid substrate PA, providing a membrane mimic for catalysis
Saccharomyces cerevisiae
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
3.1.3.4
expression of lipins 1-3 in HEK-293 cells
Mus musculus
3.1.3.4
gene PAH1, expression in Escherichia coli
Saccharomyces cerevisiae
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
3.1.3.4
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
3.1.3.4
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
3.1.3.4
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
3.1.3.4
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
3.1.3.4
additional information
generation of a pah1DELTA mutant, phenotype, overview
Saccharomyces cerevisiae
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.3.4
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
3.1.3.4
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
3.1.3.4
phytosphingosine
inhibition of PAH1
Saccharomyces cerevisiae
3.1.3.4
sphinganine
inhibition of PAH1
Saccharomyces cerevisiae
3.1.3.4
sphingosine
inhibition of PAH1
Saccharomyces cerevisiae
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
3.1.3.4
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
-
3.1.3.4
cytosol
mainly
Saccharomyces cerevisiae
5829
-
3.1.3.4
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
-
3.1.3.4
membrane
association
Saccharomyces cerevisiae
16020
-
Metals/Ions (protein specific)
EC Number
Metals/Ions
Commentary
Organism
Structure
3.1.3.4
Mg2+
dependent on
Saccharomyces cerevisiae
Molecular Weight [Da] (protein specific)
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
3.1.3.4
95000
-
1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE
Saccharomyces cerevisiae
3.1.3.4
124000
-
1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE
Saccharomyces cerevisiae
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
3.1.3.4
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
-
-
?
3.1.3.4
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
-
-
?
3.1.3.4
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
-
-
?
Posttranslational Modification (protein specific)
EC Number
Posttranslational Modification
Commentary
Organism
3.1.3.4
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) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.1.3.4
a 3-sn-phosphatidate + H2O
-
693238
Mus musculus
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
a 3-sn-phosphatidate + H2O
-
693238
Homo sapiens
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
a 3-sn-phosphatidate + H2O
-
693238
Saccharomyces cerevisiae
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
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
693238
Mus musculus
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
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
693238
Saccharomyces cerevisiae
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
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
693238
Homo sapiens
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
Subunits (protein specific)
EC Number
Subunits
Commentary
Organism
3.1.3.4
monomer
1 * 95000, about, PAH1, sequence calculation, 1 * 124000, PAH1, SDS-PAGE
Saccharomyces cerevisiae
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
3.1.3.4
7
7.5
-
Saccharomyces cerevisiae