BRENDA - Enzyme Database

Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic acid phosphatase, lipin 1

Harris, T.E.; Huffman, T.A.; Chi, A.; Shabanowitz, J.; Hunt, D.F.; Kumar, A.; Lawrence, J.C.; J. Biol. Chem. 282, 277-286 (2007)

Data extracted from this reference:

Activating Compound
EC Number
Activating Compound
Commentary
Organism
Structure
3.1.3.4
epinephrine
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly increases amounts of lipin and PAP activity in microsomes
Mus musculus
3.1.3.4
Insulin
increases the phosphorylation of multiple sites, markedly increases the amounts of lipin and PAP activity in the soluble fraction, effects of insulin are attenuated by rapamycin or by inhibiting PI 3 kinase
Mus musculus
3.1.3.4
additional information
fasting increases Mg2+-dependent PAP activity in livers from wild type animals by 2fold; insulin increases the phosphorylation of multiple sites e.g. at Ser106, insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity, overview
Mus musculus
3.1.3.4
oleic acid
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly increases amounts of lipin and PAP activity in microsomes
Mus musculus
Application
EC Number
Application
Commentary
Organism
3.1.3.4
medicine
loss of PAP activity contributes to fatty liver dystrophy phenotype. Insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity
Mus musculus
Cloned(Commentary)
EC Number
Commentary
Organism
3.1.3.4
HA-tagged forms of wild-type and mutant lipin proteins overexpressed in HEK-293 cells. Expression of HA-lipin in 3T3-L1 adipocytes by adenoviral mediated gene transfer
Mus musculus
Engineering
EC Number
Amino acid exchange
Commentary
Organism
3.1.3.4
G84R
PAP activity is ca. 20% that of the wild-type enzyme; site-directed mutagenesis, the mutant shows a 80% reduced activity compared to the wild-type lipin 1
Mus musculus
3.1.3.4
additional information
removing the COOH-terminal 15 amino acids from lipin does not significantly affect PAP activity, whereas removing an additional 37 amino acids results in a striking reduction in activity. Deleting the entire CLIP domain by COOH-terminal truncation abolishes PAP activity. Deleting the NLIP domain dramatically decreases PAP activity; the activity of the lipin protein, in which the catalytic Asp in the HAD domain is mutated to Glu, is negligible, lipin 1-deficient fld/fld mice contain much less Mg2+-dependent phosphatidic acid phosphatase activity than tissues from wild type mice, fld phenotype, overview
Mus musculus
3.1.3.4
S106A
increases electrophoretic mobility of lipin but abolishes the shift in electrophoretic mobility produced by insulin
Mus musculus
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.3.4
epinephrine
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly decreases amounts of lipin and PAP activity in the soluble fraction
Mus musculus
3.1.3.4
Insulin
markedly decreases the amounts of lipin and PAP activity in microsomes, effects of insulin are attenuated by rapamycin or by inhibiting PI 3 kinase
Mus musculus
3.1.3.4
additional information
epinephrine and oleic acid promote dephosphorylation of lipin 1, insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity, overview
Mus musculus
3.1.3.4
oleic acid
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly decreases amounts of lipin and PAP activity in the soluble fraction
Mus musculus
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
3.1.3.4
cytosol
the less phosphorylated enzyme forms are located in the cytosol
Mus musculus
5829
-
3.1.3.4
membrane
; the more phosphorylated enzyme forms are associated to membranes
Mus musculus
16020
-
3.1.3.4
microsome
-
Mus musculus
-
-
3.1.3.4
soluble
-
Mus musculus
-
-
Metals/Ions
EC Number
Metals/Ions
Commentary
Organism
Structure
3.1.3.4
Mg2+
dependent on; required
Mus musculus
Molecular Weight [Da]
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
3.1.3.4
30000
-
NH2-terminal region, including the conserved NLIP domain present, immunoprecipitation
Mus musculus
3.1.3.4
45000
-
conserved CLIP domain present, immunoprecipitation
Mus musculus
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
phosphatidic acid + H2O
Mus musculus
insulin and epinephrine control lipin 1 primarily by changing localization rather than intrinsic PAP activity, overview
1,2-dioleoyl-sn-glycerol + phosphate
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.1.3.4
Mus musculus
Q91ZP3
; heterozygous BALB/cByJ-fld/+ mice
-
Posttranslational Modification
EC Number
Posttranslational Modification
Commentary
Organism
3.1.3.4
phosphoprotein
identification of fifteen phosphorylation sites by mass spectrometric analysis
Mus musculus
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.3.4
3T3-L1 cell
-
Mus musculus
-
3.1.3.4
adipocyte
-
Mus musculus
-
3.1.3.4
brain
; fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
3.1.3.4
heart
; fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
3.1.3.4
kidney
; fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
3.1.3.4
liver
; fatty liver dystrophy; Mg2+-dependent PAP activity from fatty liver dystrophy mice is approximately half of that measured in wild-type
Mus musculus
-
3.1.3.4
lung
fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
3.1.3.4
skeletal muscle
; fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.1.3.4
phosphatidic acid + H2O
-
680814
Mus musculus
1,2-dioleoyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
phosphatidic acid + H2O
insulin and epinephrine control lipin 1 primarily by changing localization rather than intrinsic PAP activity, overview
680814
Mus musculus
1,2-dioleoyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
phosphatidic acid + H2O
-
680814
Mus musculus
phosphate + diacylglycerol
-
-
-
?
Temperature Optimum [°C]
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
3.1.3.4
30
-
assay at
Mus musculus
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
3.1.3.4
7
-
assay at
Mus musculus
Activating Compound (protein specific)
EC Number
Activating Compound
Commentary
Organism
Structure
3.1.3.4
epinephrine
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly increases amounts of lipin and PAP activity in microsomes
Mus musculus
3.1.3.4
Insulin
increases the phosphorylation of multiple sites, markedly increases the amounts of lipin and PAP activity in the soluble fraction, effects of insulin are attenuated by rapamycin or by inhibiting PI 3 kinase
Mus musculus
3.1.3.4
additional information
fasting increases Mg2+-dependent PAP activity in livers from wild type animals by 2fold; insulin increases the phosphorylation of multiple sites e.g. at Ser106, insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity, overview
Mus musculus
3.1.3.4
oleic acid
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly increases amounts of lipin and PAP activity in microsomes
Mus musculus
Application (protein specific)
EC Number
Application
Commentary
Organism
3.1.3.4
medicine
loss of PAP activity contributes to fatty liver dystrophy phenotype. Insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity
Mus musculus
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
3.1.3.4
HA-tagged forms of wild-type and mutant lipin proteins overexpressed in HEK-293 cells. Expression of HA-lipin in 3T3-L1 adipocytes by adenoviral mediated gene transfer
Mus musculus
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
3.1.3.4
G84R
PAP activity is ca. 20% that of the wild-type enzyme; site-directed mutagenesis, the mutant shows a 80% reduced activity compared to the wild-type lipin 1
Mus musculus
3.1.3.4
additional information
removing the COOH-terminal 15 amino acids from lipin does not significantly affect PAP activity, whereas removing an additional 37 amino acids results in a striking reduction in activity. Deleting the entire CLIP domain by COOH-terminal truncation abolishes PAP activity. Deleting the NLIP domain dramatically decreases PAP activity; the activity of the lipin protein, in which the catalytic Asp in the HAD domain is mutated to Glu, is negligible, lipin 1-deficient fld/fld mice contain much less Mg2+-dependent phosphatidic acid phosphatase activity than tissues from wild type mice, fld phenotype, overview
Mus musculus
3.1.3.4
S106A
increases electrophoretic mobility of lipin but abolishes the shift in electrophoretic mobility produced by insulin
Mus musculus
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
3.1.3.4
epinephrine
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly decreases amounts of lipin and PAP activity in the soluble fraction
Mus musculus
3.1.3.4
Insulin
markedly decreases the amounts of lipin and PAP activity in microsomes, effects of insulin are attenuated by rapamycin or by inhibiting PI 3 kinase
Mus musculus
3.1.3.4
additional information
epinephrine and oleic acid promote dephosphorylation of lipin 1, insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity, overview
Mus musculus
3.1.3.4
oleic acid
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly decreases amounts of lipin and PAP activity in the soluble fraction
Mus musculus
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
3.1.3.4
cytosol
the less phosphorylated enzyme forms are located in the cytosol
Mus musculus
5829
-
3.1.3.4
membrane
; the more phosphorylated enzyme forms are associated to membranes
Mus musculus
16020
-
3.1.3.4
microsome
-
Mus musculus
-
-
3.1.3.4
soluble
-
Mus musculus
-
-
Metals/Ions (protein specific)
EC Number
Metals/Ions
Commentary
Organism
Structure
3.1.3.4
Mg2+
dependent on; required
Mus musculus
Molecular Weight [Da] (protein specific)
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
3.1.3.4
30000
-
NH2-terminal region, including the conserved NLIP domain present, immunoprecipitation
Mus musculus
3.1.3.4
45000
-
conserved CLIP domain present, immunoprecipitation
Mus musculus
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
phosphatidic acid + H2O
Mus musculus
insulin and epinephrine control lipin 1 primarily by changing localization rather than intrinsic PAP activity, overview
1,2-dioleoyl-sn-glycerol + phosphate
-
-
?
Posttranslational Modification (protein specific)
EC Number
Posttranslational Modification
Commentary
Organism
3.1.3.4
phosphoprotein
identification of fifteen phosphorylation sites by mass spectrometric analysis
Mus musculus
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.3.4
3T3-L1 cell
-
Mus musculus
-
3.1.3.4
adipocyte
-
Mus musculus
-
3.1.3.4
brain
; fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
3.1.3.4
heart
; fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
3.1.3.4
kidney
; fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
3.1.3.4
liver
; fatty liver dystrophy; Mg2+-dependent PAP activity from fatty liver dystrophy mice is approximately half of that measured in wild-type
Mus musculus
-
3.1.3.4
lung
fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
3.1.3.4
skeletal muscle
; fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mus musculus
-
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
phosphatidic acid + H2O
-
680814
Mus musculus
1,2-dioleoyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
phosphatidic acid + H2O
insulin and epinephrine control lipin 1 primarily by changing localization rather than intrinsic PAP activity, overview
680814
Mus musculus
1,2-dioleoyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
phosphatidic acid + H2O
-
680814
Mus musculus
phosphate + diacylglycerol
-
-
-
?
Temperature Optimum [°C] (protein specific)
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
3.1.3.4
30
-
assay at
Mus musculus
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
3.1.3.4
7
-
assay at
Mus musculus