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Information on EC 3.1.3.4 - phosphatidate phosphatase and Organism(s) Mus musculus and UniProt Accession Q99JY8
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3.1.3.4 phosphatidate phosphataseIUBMB Comments
This enzyme catalyses the Mg2+-dependent dephosphorylation of a 1,2-diacylglycerol-3-phosphate, yielding a 1,2-diacyl-sn-glycerol (DAG), the substrate for de novo lipid synthesis via the Kennedy pathway and for the synthesis of triacylglycerol. In lipid signalling, the enzyme generates a pool of DAG to be used for protein kinase C activation. The mammalian enzymes are known as lipins.
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Word Map
- 3.1.3.4
- phospholipid
- triacylglycerols
- phospholipase
-
lipins
- phosphatidylcholine
- triglyceride
- propranolol
- adipose
-
lysophosphatidic
- glycerolipids
- acyltransferase
- adipocyte
-
lipogenesis
-
lipogenic
- sphingosine
- pkc
- steatosis
- lipodystrophy
- rhabdomyolysis
- cytidylyltransferase
-
mg2+-independent
- sphingosine-1-phosphate
- phosphatidylethanol
-
diradylglycerol
-
bromoenol
-
transphosphatidylation
-
kennedy
- cdp-diacylglycerol
- sn-glycerol
-
argonaut
- 1,2-diacylglycerol
-
sphingoid
-
srebf1
-
dgats
-
pirnas
- glycerolphosphate
- pc-plc
-
plectonema
-
ctp:phosphocholine
-
plasticity-related
- acaca
-
prophenoloxidase
-
cholinephosphotransferase
-
phosphatidylcholine-specific
- sn-glycerol-3-phosphate
- medicine
- analysis
- drug development
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
phosphatidate phosphohydrolase, lipin-1, lpin1, pap-1, lipin1, phosphatidate phosphatase, lipin 1, prg-1, phosphatidic acid phosphohydrolase, pa phosphatase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acid phosphatidyl phosphatase
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-
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ecto-PAPase
-
-
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ecto-phosphatidic acid phosphohydrolase
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-
-
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Germ cell guidance factor
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-
-
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lipin 1
lipin-1alpha
Mg2+-dependent phosphatidic acid phosphatase
PA phosphatase
PAP
phosphatidate phosphohydrolase
phosphatidic acid phosphatase
phosphatidic acid phosphohydrolase
Wunen protein
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-
-
-
additional information
PA phosphatase
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-
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PAP
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-
-
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phosphatidate phosphohydrolase
-
-
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phosphatidic acid phosphatase
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-
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phosphatidic acid phosphohydrolase
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-
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-
additional information
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the enzyme belongs to the lipid phosphate phosphatase family
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
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-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
diacylglycerol-3-phosphate phosphohydrolase
This enzyme catalyses the Mg2+-dependent dephosphorylation of a 1,2-diacylglycerol-3-phosphate, yielding a 1,2-diacyl-sn-glycerol (DAG), the substrate for de novo lipid synthesis via the Kennedy pathway and for the synthesis of triacylglycerol. In lipid signalling, the enzyme generates a pool of DAG to be used for protein kinase C activation. The mammalian enzymes are known as lipins.
CAS REGISTRY NUMBER
COMMENTARY
9025-77-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dihydro-sphingosine-1-phosphate + H2O
dihydro-sphingosine + phosphate
-
all LPPs
-
-
?
phosphatidic acid + H2O
1,2-diacylglycerol + phosphate
-
lipid phosphate phosphatase-1 regulates lysophosphatidate-induced fibroblast migration by controlling phospholipase D2-dependent phosphatidate generation, LPP1 expression decreases PLD activity and PA accumulation after stimulating fibroblasts with either LPA or PDGF, but PLD-dependent PA formation Is only required for LPA-induced fibroblast migration, overview
-
-
?
phosphatidic acid + H2O
diacylglycerol + phosphate
-
-
-
-
?
lysophosphatidic acid + H2O
monoacylglycerol + phosphate
LPP3 regulates intracellular and extracellular lysophosphatidic acid and sphingosine-1-phosphate signalling through the dephosphorylation of these bioactive lipids
-
-
?
sphingosine-1-phosphate + H2O
sphingosine + phosphate
LPP3 regulates intracellular and extracellular lysophosphatidic acid and sphingosine-1-phosphate signalling through the dephosphorylation of these bioactive lipids
-
-
?
1,2-dioleoyl-sn-glycerol-3 phosphate
1,2-dioleoyl-sn-glycerol + phosphate
-
-
-
-
?
1,2-dioleoyl-sn-glycerol-3 phosphate
1,2-dioleoyl-sn-glycerol + phosphate
-
-
-
?
1,2-dioleoyl-sn-glycerol-3 phosphate
1,2-dioleoyl-sn-glycerol + phosphate
insulin and epinephrine control lipin 1 primarily by changing localization rather than intrinsic PAP activity, overview
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
-
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
key enzyme in glycerolipid synthesis, diacylglycerol is direct precursor of triacylglycerol, phosphoatidylcholine, and phosphatidylethanolamine. Lipin-1 influences lipid homeostasis and plays a critical role in adipocyte development with lipin-1A and lipin-1B having distinct purposes in the process, overview. Phosphorylation plays an important role in modulation of enzyme activity, overview
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
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 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
lipin 1 is a bifunctional intracellular protein that regulates fatty acid metabolism in the nucleus via interactions with DNA-bound transcription factors and at the endoplasmic reticulum as a phosphatidic acid phosphohydrolase enzyme to catalyze the penultimate step in triglyceride synthesis. Lipin 2 plays an important role as a hepatic PAP-1 enzyme
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
lipin-1 plays a critical role in the perturbation of hepatic insulin signaling
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
lipin-2 is negatively regulated by phosphorylation during mitosis
-
-
?
lysophosphatidic acid + H2O
monoacylglycerol + phosphate
-
-
-
-
?
phosphatidic acid + H2O
1,2-diacyl-sn-glycerol + phosphate
-
-
-
-
?
phosphatidic acid + H2O
1,2-diacyl-sn-glycerol + phosphate
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lipin-1, lipin-2, and lipin-3
-
-
?
phosphatidic acid + H2O
1,2-diacyl-sn-glycerol + phosphate
-
diacylglycerol is the necessary precursor for the synthesis of triacylglycerols, phosphatidylcholine and phosphatidylethanolamine
-
-
?
sphingosine 1-phosphate + H2O
sphingosine + phosphate
-
-
-
-
?
additional information
?
-
-
LPP is involved in regulation of bioactive lipids acting in signalling pathways, LPP-1 regulates lysophosphatidic acid- and platelet-derived-growth-factor-induced cell migration via the p42/p44 MAPK pathway, overview
-
-
?
additional information
?
-
-
LPP is involved in regulation of bioactive lipids acting in signalling pathways, physiological roles of enzyme activity at the cell surface and intracellularly, overview
-
-
?
additional information
?
-
-
LPP is involved in regulation of bioactive lipids acting in signalling pathways, thus the enzyme is involved in cell division, cytoskeletal rearrangement, Ca2+ transients, and membrane movement, the enzyme is also able to hydrolyze extracellular substrates, lysophosphatidic acid and sphingosine 1-phosphate, involved in wound repair and tumor growth, metabolism of lysophosphatidic acid and sphingosine 1-phosphate, intra- and extracellular function, overview
-
-
?
additional information
?
-
-
LPP is involved in regulation of bioactive lipids, physiological roles of LPP isozymes
-
-
?
additional information
?
-
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the enzyme regulates the level of phosphorylated lipids acting as growth factors or second messengers, the enzyme is involved in lipid signaling pathways
-
-
?
additional information
?
-
-
lipin-1 Smp2 exhibits phosphatidate phosphatase type-1 activity, which plays a key role in glycerolipid synthesis
-
-
?
additional information
?
-
-
the enzyme is regulated by estrogens in the liver and the uterus, E2 downregulates the enzyme in the uterus via the estrogen receptor in a primary response, overview
-
-
?
additional information
?
-
-
hyperactivation of TORC2 exacerbates insulin resistance by enhancing expression of LIPIN1, a mammalian phosphatidic acid phosphatase for diacylglycerol synthesis, overview
-
-
?
additional information
?
-
-
lipin 2 is dynamically regulated in liver but is not a target gene of PGC-1alpha
-
-
?
additional information
?
-
-
lipin-1 operates as a transcriptional coactivator together with nuclear receptors and coactivators, e.g. PPARgamma coactivator 1alpha, i.e. PGC-1alpha, to modulate gene expression in lipid metabolism
-
-
?
additional information
?
-
-
phosphatidic acid phosphohydrolase 1 and protein kinase C are required for Toll-like receptor-4-mediated group IVA phospholipase A2 activation, regulation, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
lysophosphatidic acid + H2O
monoacylglycerol + phosphate
LPP3 regulates intracellular and extracellular lysophosphatidic acid and sphingosine-1-phosphate signalling through the dephosphorylation of these bioactive lipids
-
-
?
sphingosine-1-phosphate + H2O
sphingosine + phosphate
LPP3 regulates intracellular and extracellular lysophosphatidic acid and sphingosine-1-phosphate signalling through the dephosphorylation of these bioactive lipids
-
-
?
1,2-dioleoyl-sn-glycerol-3 phosphate
1,2-dioleoyl-sn-glycerol + phosphate
insulin and epinephrine control lipin 1 primarily by changing localization rather than intrinsic PAP activity, overview
-
-
?
lysophosphatidic acid + H2O
monoacylglycerol + phosphate
-
-
-
-
?
phosphatidic acid + H2O
1,2-diacylglycerol + phosphate
-
lipid phosphate phosphatase-1 regulates lysophosphatidate-induced fibroblast migration by controlling phospholipase D2-dependent phosphatidate generation, LPP1 expression decreases PLD activity and PA accumulation after stimulating fibroblasts with either LPA or PDGF, but PLD-dependent PA formation Is only required for LPA-induced fibroblast migration, overview
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
key enzyme in glycerolipid synthesis, diacylglycerol is direct precursor of triacylglycerol, phosphoatidylcholine, and phosphatidylethanolamine. Lipin-1 influences lipid homeostasis and plays a critical role in adipocyte development with lipin-1A and lipin-1B having distinct purposes in the process, overview. Phosphorylation plays an important role in modulation of enzyme activity, overview
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
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 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
lipin 1 is a bifunctional intracellular protein that regulates fatty acid metabolism in the nucleus via interactions with DNA-bound transcription factors and at the endoplasmic reticulum as a phosphatidic acid phosphohydrolase enzyme to catalyze the penultimate step in triglyceride synthesis. Lipin 2 plays an important role as a hepatic PAP-1 enzyme
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
lipin-1 plays a critical role in the perturbation of hepatic insulin signaling
-
-
?
a 3-sn-phosphatidate + H2O
a 1,2-diacyl-sn-glycerol + phosphate
-
lipin-2 is negatively regulated by phosphorylation during mitosis
-
-
?
additional information
?
-
-
LPP is involved in regulation of bioactive lipids acting in signalling pathways, LPP-1 regulates lysophosphatidic acid- and platelet-derived-growth-factor-induced cell migration via the p42/p44 MAPK pathway, overview
-
-
?
additional information
?
-
-
LPP is involved in regulation of bioactive lipids acting in signalling pathways, physiological roles of enzyme activity at the cell surface and intracellularly, overview
-
-
?
additional information
?
-
-
LPP is involved in regulation of bioactive lipids acting in signalling pathways, thus the enzyme is involved in cell division, cytoskeletal rearrangement, Ca2+ transients, and membrane movement, the enzyme is also able to hydrolyze extracellular substrates, lysophosphatidic acid and sphingosine 1-phosphate, involved in wound repair and tumor growth, metabolism of lysophosphatidic acid and sphingosine 1-phosphate, intra- and extracellular function, overview
-
-
?
additional information
?
-
-
LPP is involved in regulation of bioactive lipids, physiological roles of LPP isozymes
-
-
?
additional information
?
-
-
the enzyme regulates the level of phosphorylated lipids acting as growth factors or second messengers, the enzyme is involved in lipid signaling pathways
-
-
?
additional information
?
-
-
lipin-1 Smp2 exhibits phosphatidate phosphatase type-1 activity, which plays a key role in glycerolipid synthesis
-
-
?
additional information
?
-
-
the enzyme is regulated by estrogens in the liver and the uterus, E2 downregulates the enzyme in the uterus via the estrogen receptor in a primary response, overview
-
-
?
additional information
?
-
-
hyperactivation of TORC2 exacerbates insulin resistance by enhancing expression of LIPIN1, a mammalian phosphatidic acid phosphatase for diacylglycerol synthesis, overview
-
-
?
additional information
?
-
-
lipin 2 is dynamically regulated in liver but is not a target gene of PGC-1alpha
-
-
?
additional information
?
-
-
lipin-1 operates as a transcriptional coactivator together with nuclear receptors and coactivators, e.g. PPARgamma coactivator 1alpha, i.e. PGC-1alpha, to modulate gene expression in lipid metabolism
-
-
?
additional information
?
-
-
phosphatidic acid phosphohydrolase 1 and protein kinase C are required for Toll-like receptor-4-mediated group IVA phospholipase A2 activation, regulation, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
lipin 1-mediated repression of nuclear factor of activated T-cells transcriptional activity occurs after nuclear factor of activated T-cells mobilization and activation by calcium
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
epinephrine
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly decreases amounts of lipin and PAP activity in the soluble fraction
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
-
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
shRNA
-
lipin 2 shRNA treatment significantly reduces hepatocyte PAP-1 activity in both wild-type and fld hepatocytes
-
siRNA
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rat2 fibroblasts treated with siRNA for LPP1 show about a 60% decrease in mRNA for the targeted LPP
-
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
-
additional information
-
mitotic phosphorylation of lipin 2 inhibits its phosphatidic acid phosphatase activity
-
additional information
-
PAP-1 chemical inhibition does not reduce the synergistic activation of group IVA phospholipase A2
-
additional information
-
phosphorylation inhibits activity, phosphorylation of lipin 1 on multiple sites correlates with a decrease of its microsomal-bound pool
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
epinephrine
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly increases amounts of lipin and PAP activity in microsomes
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
-
oleic acid
promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly increases amounts of lipin and PAP activity in microsomes
additional information
fasting increases Mg2+-dependent PAP activity in livers from wild type animals by 2fold
-
additional information
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
-
additional information
-
hepatic lipin 2 protein content is markedly increased by lipin 1 deficiency, food deprivation, and obesity, often independent of changes in steady-state mRNA levels. Fasting induces expression of Lpin1 and Lpin2 in wild-type and PGC-1alpha-deficient mice
-
additional information
-
hyperactivated TORC2 enhances expression of lipin1. Diet-induced or genetic obesity increases LIPIN1 expression in mouse liver, and TORC2 is responsible for its transcriptional activation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics of the PAP1 activities of the three lipin proteins, surface dilution kinetic model using micelles of Triton X-100, each lipin exhibits a strong positive cooperativity for phosphatidic acid
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
expression levels in uteri and livers of nondiabetic C57BL6 and CD-1 mice, and diabetic NOD mice and Pd-NOD mice, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
lipin-2, in circulating red blood cells, at ca. 10% of the levels observed in liver
-
low levels of lipin-2, in bone and bone marrow, at 1020% the levels in liver
-
lipin-2, in whole spleen and the white blood cell fraction of spleen, at ca. 10% of the levels observed in liver
-
predominantly in the glandular and luminal epithelium, apical region, overview
additional information
-
lipin-1 accounts for all of the PAP1 activity in adipose tissue and skeletal muscle
fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
-
embryonic, derived from LPP-1 overexpression mutant and wild-type mice
fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
Mg2+-dependent PAP activity from fatty liver dystrophy mice is approximately half of that measured in wild-type
-
lipin 2 is enriched in fatty liver dystrophic (fld) mice, whereas lipin 1 and lipin 3 protein is absent
fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice
-
lipin-1 accounts for all of the PAP1 activity in adipose tissue and skeletal muscle
additional information
-
tissue expression patterns of lipin isozymes, overview, lipin-1 is responsible for PAP1 activity in adipose tissue and skeletal muscle
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
the less phosphorylated enzyme forms are located in the cytosol
-
lipin-1 and lipin-2 are soluble proteins that can also be localized to the nucleus or associate with endoplasmic reticulum membranes
-
wild-type and lipin-2 are present at similar levels in cytosolic and membrane fractions in the absence of oleate
-
the enzyme binds to the cytosolic side of the membranes, overview
-
lipin-1 and lipin-2 are soluble proteins that can also be localized to the nucleus or associate with endoplasmic reticulum membranes
the more phosphorylated enzyme forms are associated to membranes
-
wild-type and lipin-2 are present at similar levels in cytosolic and membrane fractions in the absence of oleate, and it translocates to the membrane fraction with increasing levels of oleate
-
the transcriptional coactivator function of lipin1beta necessarily requires localization in the nucleus
-
the enzymes act on the cytoplasmic and the cell surface side of the membrane
additional information
-
the enzyme also hydrolyses extracellularly located substrates
-
additional information
-
20% of transfected 3T3-L1 adipocyte cells contain lipin-1alpha exclusively in the nucleus, in more than 50% of cells lipin-1alpha is present in similar amounts in the cytoplasm and the nucleus. 14-3-3 proteins promote cytoplasmic localization of lipin-1alpha
-
additional information
-
in embryonic cortical neurons, lipin-1beta shows exclusively cytoplasmic localization. In SH-SY5Y clones, ectopic lipin-1a exhibits both nuclear and cytosolic localization, with a higher concentration in the nucleus, whereas lipin-1alpha is concentrated in the cytoplasm in HEK-93A cells. Sumoylation facilitates the nuclear localization and transcriptional coactivator behavior of lipin-1alpha in embryonic cortical neurons
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
LPP3 deficiency, specifically targeted at vascular cell types, induces endothelial permeability, promotes leukocyte adhesion to endothelial cells and stimulates smooth muscle cell proliferation. Hepatocyte-specific Plpp3 deficiency, by modulating the plasma lipidome, exacerbates atherosclerosis development in Apoe-/-x01mice
physiological function
malfunction
physiological function
physiological function
lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice
physiological function
LPP3 activity is crucial for vascular and heart development
physiological function
LPP3 regulates intracellular and extracellular lysophosphatidic acid and sphingosine-1-phosphate signalling through the dephosphorylation of these bioactive lipids
malfunction
-
in fat pads from mice deficient for lipin 1 (fld mice) and in 3T3-L1 adipocytes depleted of lipin 1 there is increased expression of several nuclear factor of activated T-cells target genes including TNFalpha, resistin, FABP4 and PPARgamma. Lipin 1 with the highly conserved amino-terminal NLIP domain deleted (DELTAN) is capable of both interaction and repression
malfunction
-
lipin 1 deficiency does not affect PAP-1 activity in neonatal mice and leads to hepatic triglyceride accumulation. Loss of lipin 2 markedly impairs hepatocyte PAP-1 activity but does not affect basal rates of triglyceride synthesis. Lipin 2 knockdown abrogates triglyceride synthesis under conditions of increased fatty acid availability
malfunction
-
lipin 1 gene is mutated in the fatty liver dystrophy mouse, which displays features of generalized lipodystrophy, characterized by significant reduction in the adipose tissue mass and in the cellular lipid droplet content
malfunction
-
lipin-1 deficiency causes lipodystrophy, neonatal fatty liver, peripheral neuropathy, insulin resistance, and increased susceptibility to atherosclerosis
malfunction
-
lipin-1 deficiency produces lipodystrophy. In fatty liver dystrophy mice, occurrence of fatty liver and hypertriglyceridemia during the neonatal period, and peripheral neuropathy, which progresses throughout adulthood. Fatty liver dystrophy mice are lipodystrophic, develop insulin resistance, and have increased susceptibility to atherosclerosis. Lipin-2 cannot compensate for lipin-1 function in adipose tissue of fatty liver dystrophy mice
malfunction
-
LPP1 hypomorph mice (Ppap2atr/tr) have depleted LPP1 expression in most tissues. Lysophosphatidate concentrations in the plasma are higher in Ppap2atr/tr mice compared with controls. Embryos from LPP3 knockout mice fail to form a chorio-allantoic placenta and yolk sac vasculature and some embryos show shortening of the anterior-posterior axis similar to axin deficiency, a critical regulator of Wnt signaling. LPP2 knockout mice are fertile and viable with no obvious phenotype
malfunction
-
nuclear localization is abrogated by mutating the consensus sumyolation motifs. Sumoylation site mutant of lipin-1alpha loses the capacity to coactivate the transcriptional (co-) activators PGC-1alpha and MEF2, consistent with its nuclear exclusion
malfunction
-
fatty liver dystrophy mice carrying mutations within the lipin 1 gene display life-long deficiency in adipogenesis, insulin resistance, neonatal hepatosteatosis and hypertriglyceridemia, as well as increased atherosclerosis susceptibility. Lipin-1 deficiency results in the activation of the sterol regulatory element binding protein 1 and its target genes as well as in very high expression levels of stearoyl-CoA desaturase-1 and apoA-IV. Acute lipin-1 deficiency in the mouse liver abolishes fasting-induced activation of Ppara and several PPARalpha/PGC-1alpha target genes, such as Acadvl, Acadm and Fabp1
physiological function
-
endogenous 14-3-3 proteins interact with lipin-1alpha in HEK293 cells, overexpression of 14-3-3 promotes the cytoplasmic localization of lipin-1 in 3T3-L1 adipocytes. Effect of 14-3-3 is mediated through a serine-rich domain in lipin-1. Insulin stimulates interaction with 14-3-3 and cytoplasmic localization of lipin-1alpha in 3T3-L1 adipocytes
physiological function
-
has essential roles in lipid droplet and phospholipid metabolism
physiological function
-
key role for lipin-1 in adipocyte differentiation and lipid biosynthesis
physiological function
-
lipin 1 is a potentially important link between triacylglycerol synthesis and adipose tissue inflammation. Lipin 1 represses nuclear factor of activated T-cells c4 transcriptional activity through protein-protein interaction and in the context of at least two different composite elements. Specific residues required for interaction with lipin 1 are contained within the RHD/DNA binding domain and carboxy terminus of nuclear factor of activated T-cells c4. Lipin 1 is present at the promoters of nuclear factor of activated T-cells c4 transcriptional targets in vivo. Lipin 1 protein and total PAP activity are decreased with increasing adiposity in the visceral, but not subcutaneous, fat pads of ob/ob mice. Lipin 1 can act to repress or activate transcription factors. Lipin 1 interacts with nuclear factor of activated T-cells c4 bound to DNA and is present at the promoters of nuclear factor of activated T-cells target genes. Lipin 1 recruits a histone deacetylase to repress nuclear factor of activated T-cells c4 transcription
physiological function
-
lipin 2 plays an important role as a hepatic PAP-1 enzyme. Lipin 2 overexpression increases PAP-1 activity in HepG2 cells. Increased hepatic expression of lipin 2 plays a role in increased hepatic triglyceride synthesis rates in ob/ob mice
physiological function
-
lipin-1 accounts for all of the PAP activity in adipose tissue and skeletal muscle, but only part of the activity in liver, heart, kidney, and brain. Enhanced lipin-1 expression in adipose tissue or skeletal muscle promotes obesity. Lipin-2 and/or lipin-3 are capable of promoting VLDL synthesis and secretion
physiological function
-
lipin-1 may be a mediator of glucocorticoid effects in conditions such as fasting and obesity, genetic variations in this response may contribute to interindividual variations in lipin-1 expression levels. Glucocorticoid-induced Lpin1 regulation leads to increased protein and PAP1 activity
physiological function
-
lipin-1alpha may act as a sumoylation-regulated transcriptional coactivator in brain. Sumoylated forms of lipin-1 in muscle and liver are only marginally present. Lipin-1 (including both the alpha and beta isoforms) is modified by sumoylation at two consensus sumoylation sites, is sumoylated at relatively high levels in brain. No sumoylation of the related proteins lipin-2 and lipin-3
physiological function
-
lipin-2 has transcriptional coactivator activity for peroxisome proliferator-activated receptor-response elements similar to lipin-1. Lipin-1A activates PPRE-luciferase expression ca. 2fold
physiological function
-
LPP3 contains arginine-glycine-glutamate (RGE) cell adhesion sequence, but murine LPP3 also interacts with alpha5beta1 and alphavalpha3 integrins. Transgenic mice that overexpress LPP1 demonstrate no significant differences in circulating lysophosphatidate concentrations compared with control mice. LPP3 functions as a Wnt signaling antagonist. Mice that overexpress LPP1 have decreased birth weight, sparse curly hair, and defective spermatogenesis causing infertility. LPP1 controls lysophosphatidate removal from the blood, which increases circulating lysophosphatidate levels. LPP2 regulates the timing of S-phase entry, but it is not essential for cell cycle progression
physiological function
-
LPP3 yields an 8fold increase in luciferase (lymphoid enhancer binding factor 1) activity
physiological function
-
physiologically relevant increases in LPP1 activity in mouse embryonic fibroblasts (isolated from transgenic mice with 20 gene copies of LPP1) reduces lysophosphatidic acid- and platelet-derived growth factor-activation of ERK-1/2 and migration, resulting from down-regulation of typical proteinkinase C isoform(s) which are required for regulation of cell migration
physiological function
-
lipin proteins play a dual function in lipid metabolism by acting as phosphatidate phosphatase enzymes and as transcriptional regulators. Lipin-1 is a key integrator of hormonal signals to the liver in diabetic dyslipidemia. Lipin-1 also induces the expression of key adipogenic transcription factors including PPARgamma and C/EBPalpha. Isoforms lipin-1alpha and lipin-1beta exert complementary roles in adipocyte differentiation. While lipin-1alpha induces the expression of adipogenic transcription factors, lipin-1beta induces the expression of lipid synthesis genes encoding, e.g., fatty acid synthase and diacylglycerol acyltransferase. Hepatic very low density lipoprotein synthesis and secretion is highly influenced by the expression of lipin-1. Membrane dynamics (conveyor) for very low density lipoprotein assembly/secretion are regulated by lipin-1
physiological function
-
the lipin 1 polybasic motif is critical for lipin1beta function in phospholipid and neutral lipid metabolism. Lipin1beta also functions as transcriptional coactivator. Both the transcriptional and metabolic functions of lipin 1 are required for full complementation of the adipogenic differentiation of lipin-deficient MEF cells. Lipin1 is also an amplifier of PGC-1alpha, a nuclear coactivator of PPAR-alpha responsive gene transcription
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PLPP3_MOUSE
312
6
35216
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
NH2-terminal region, including the conserved NLIP domain present, immunoprecipitation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 31000-36000, recombinant Myc-tagged and/or FLAG-tagged LPP1 or LLP3, SDS-PAGE
additional information
-
LPP1 monomers might exist in equilibrium with oligomeric LPP1, the LPP1 monomer is inactive, endogenous LPP2 and LPP3 form a complex
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
phosphoprotein
sumoylation
-
isoforms lipin-1alpha and lipin-1beta undergo sumoylation on two consensus sumoylation sites
glycoprotein
-
the glycosylation is not required for catalytic activity, no glycosylation of PRG-1
phosphoprotein
-
reversible phosphorylation might play a role in enzyme regulation
phosphoprotein
identification of fifteen phosphorylation sites by mass spectrometric analysis
phosphoprotein
-
mitotic phosphorylation of lipin 2 inhibits its phosphatidic acid phosphatase activity
phosphoprotein
-
phosphorylation plays an important role in modulation of enzyme activity, phosphorylation of lipin-1 and lipin-2 is associated with reduced PAP1 activity druing mitosis, phosphorylation of lipin-1, mainly at Ser106, influences its subcellular localization, dephosphorylation of lipin-1 in response to oleic acid and epinephrine
phosphoprotein
-
serine 106 residue of lipin-1 and lipin-2 is a major site of phosphorylation
phosphoprotein
-
insulin-stimulated phosphorylation sites in lipin-1 are at Ser106, Ser634, and Ser720
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D398E
-
catalytically inactive PAP enzymes with a mutation in a conserved NLIP domain residue fail to complement phenotypes caused by the pah1DELTA mutation
D400E
-
catalytically inactive PAP enzymes with a mutation in a conserved NLIP domain residue fail to complement phenotypes caused by the pah1DELTA mutation
D712E
G170A
-
38% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
G80R
-
catalytically inactive PAP enzymes with a mutation in a conserved NLIP domain residue fail to complement phenotypes caused by the pah1DELTA mutation
G84R
H171L
H223L
I233T
-
94% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
I706F
-
lacks enzymatic activity, retains the ability to interact with and repress nuclear factor of activated T-cells c4 transcriptional activity
I707F
-
lacks enzymatic activity, retains the ability to interact with and repress nuclear factor of activated T-cells c4 transcriptional activity
I723F
-
lacks enzymatic activity, is unable to interact with nuclear factor of activated T-cells c4 and has no repressive effect on reporter gene activity
K120R
K566R/K596R
-
blocks lipin-1alpha sumoylation. In embryonic cortical neurons or SH-SY5Y clones, almost completely loses its nuclear localization compared to wild-type, although its cytoplasmic localization remains unchanged. Retains Mg2+-dependent phosphatase activity for phosphatidic acid (C8), but not for lysophosphatidic acid (C18:1)
K599R/K626R
-
lipin-1beta mutant, is not modified by SUMO-1 in an in vitro sumoylation reaction
L106S
-
85% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
L724F
-
lacks enzymatic activity, is unable to interact with nuclear factor of activated T-cells c4 and has no repressive effect on reporter gene activity
N142Q
-
89% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate, mutation decreases the molecular weight by about 4000 Da
N276Q
-
112% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
P128I
R127K
R217K
S106A
increases electrophoretic mobility of lipin but abolishes the shift in electrophoretic mobility produced by insulin
S169T
S731D
-
PAP deficiency, does not result from impaired membrane association. Exhibits normal membrane localization
S731L
-
lipin-2 mutant, protein expression at similar levels as the wild-type, thus lack of PAP activity is not related to reduced protein levels or protein stability. PAP deficiency does not result from impaired membrane association. Shows no reduction in membrane association, in multiple trials exhibits a trend toward increased membrane localization compared with wild-type lipin-2, particularly in the absence of oleate. Shows identical coactivator activity to wild-type lipin-1A and lipin-2
T116I
-
91% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
T122S
-
97% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
T5P
-
85% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
Y168F
-
87% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
Y221W
-
51% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
additional information
D712E
-
lacks enzymatic activity, does not affect the interaction of lipin 1 and PPARalpha, but eliminates the ability of lipin 1 to interact with nuclear factor of activated T-cells c4. Also fails to repress nuclear factor of activated T-cells c4 transcriptional activity
G84R
site-directed mutagenesis, the mutant shows a 80% reduced activity compared to the wild-type lipin 1
G84R
-
causes lipodystrophy. Mutated residue is a conserved glycine in the N-LIP domain required for enzymatic activity
H171L
-
2% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
H171L
-
site-directed mutagenesis of the C2 domain conserved amino acid residue leads to reduced activity of LPP1
H223L
-
2% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
H223L
-
site-directed mutagenesis of the C3 domain conserved amino acid residue leads to reduced activity of LPP1
K120R
-
5% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
K120R
-
site-directed mutagenesis of the C1 domain conserved amino acid residue leads to reduced activity of LPP1
P128I
-
2% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
P128I
-
site-directed mutagenesis of the C1 domain conserved amino acid residue leads to reduced activity of LPP1
R127K
-
2% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
R127K
-
site-directed mutagenesis of the C1 domain conserved amino acid residue leads to reduced activity of LPP1
R217K
-
2% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
R217K
-
site-directed mutagenesis of the C3 domain conserved amino acid residue leads to reduced activity of LPP1
S169T
-
0.4% of the dephosphorylation activity of the wild-type enzyme with lysophosphatidate as substrate
S169T
-
site-directed mutagenesis of the C2 domain conserved amino acid residue leads to reduced activity of LPP1
additional information
-
construction of LPP3 or LPP1 knockout mice, the embryonic fibroblasts of these transgenic mice show diacylglycerol levels and reduced phosphatidic acid levels
additional information
-
construction of several mouse models overexpressing or lacking LPP isozymes, e.g. overexpression of LPP-1 leads to defects in fertility in female mice and to increased accumulation of diacylglycerol, LPP-2 knockout mice are fertile and viable, whereas LPP-3 knockout mice show a severe phenotype failing to form a chorio-allantoic placenta and yolk sac vasculature, in addition, mutant embryos show a shortening of the anterior-posterior axis, overview, introduction of LPP-1 into Drosophila melanogaster germ cells has no effect on the germ-cell-specific factor in vivo
additional information
-
construction of transgenic mice overexpressing the enzyme, the phenotype includes reduced body size, birth weight, and abnormalities in fur growth, decreased number of hair follicles, disrupted hair structure, and impaired spermatogenesis, phospholipid levels of mutants compared to wild-type mice, overview, ERK1/2 activation is not affected by enzyme overexpression
additional information
-
LPP-1 overexpression mutant shows inhibited cell migration of embryonic fibroblasts by reduction of lysophosphatidic acid- and platelet-derived-growth-factor-induced activation of the p42/p44 MAPK pathway, overview
additional information
-
lipin1-deficient mice show reduce fertility, phenotype, overview
additional information
-
livers of lipin-1-deficient mice exhibit normal PAP1 activity
additional information
-
LPP1 overexpressing fibroblasts show a severe inhibition of LPA-induced migration not mediated through the degradation of extracellular LPA in a woundhealing assay, overview
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
additional information
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
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
additional information
-
lipin-1-deficient fld mice show that lipin-1 accounts for all of the PAP1 activity in adipose tissue and skeletal muscle, targeted expression of lipin-1 in adipose tissue of transgenic mice leads to obesity, overview
additional information
-
livers of fld mice lacking lipin 1 exhibit normal PAP-1 activity and a 20fold increase in triglyceride levels, while the hepatic content of phosphatidate is markedly diminished in fld mice. Other phospholipids derived from phosphatidate, phosphatidylglycerol and cardiolipin, are also depleted. Hepatic lipin 2 protein content is markedly increased by lipin 1 deficiency via a posttranscriptional mechanism
additional information
-
overexpression of LIPIN1 disturbs hepatic insulin signaling, knockdown of LIPIN1 ameliorates hyperglycemia and insulin resistance by reducing diacylglycerol and PKC3 activity in db/db mice. TORC2-mediated insulin resistance is partially rescued by concomitant knockdown of LIPIN1, overview
additional information
-
PAP-1 inhibition leads to the loss of cyclooxygenase 2 expression and PGE2 release
additional information
-
mutant lipin-1alpha lacking the serine-rich domain, is excluded from the nucleus
additional information
-
mutation of IL728FF does not affect the interaction with peroxisome proliferator-activated receptor gamma2
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
coding sequence of lipin 1b subcloned downstream of the GST tag in the pEBG expression vector, transfected into 293T cells. Adenoviral constructs for HA-tagged lipin 1b
-
expression analysis of lipin-1 and lipin-2, recombinant expression of lipin-2 in Hep-G2 cells using an adenoviral vector
-
expression of Myc-tagged and/or FLAG-tagged LPP1, LLP2, and LLP3 in HEK-293 cells, overview
-
expression of the gene encoding the enzyme under control of chicken beta-actin promoter in mice embryos
-
full-length lipin1beta cDNA amplified and cloned into the pcDNA3.1-V5/His-TOPO expression vector and pSG5-FLAG-tagged expression vector. Peroxisome proliferator-activated receptor gamma2 and lipin1 overexpressed in NIH3T3 cells
-
full-length triple HA-tagged lipin 2 cloned into pCDNA3 expression construct, subcloned into the Ad-track cytomegalovirus vector, and recombined into the Ad-EASY system. Full-length cDNA for lipin 3 from pSPORT-lipin 3 expression vector
-
gene Lpp1, stable overexpression of wild-type and mutant LPP1 enzymes in Rat2 fibroblasts using a retroviral vector and puromycin selection
-
genes Lpin1, Lpin2, and Lpin3, expression analysis reveals distinct gene regulation in the hepatocytes
-
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
HEK293 cells or 3T3-L1 adipocytes transfected with wild-type or mutant lipin-1alpha lacking the serine-rich domain
-
V5 epitope-tagged lipin-1 and lipin-2 expression plasmids, transiently transfected into Hepa 16 cells. Wild-type lipin-1A and lipin-2 and mutants lipin-1A-S724L and lipin-2-S731L expressed in HEK-293 cells
-
V5-tagged lipin-1alpha, lipin-1beta, lipin-2 and lipin-3 expression vectors. HEK-293A cells transfected with plasmids expressing V5-tagged proteins. HeLa cells transfected with expression plasmids for V5-lipin-1beta and CFP-SUMO-1 or their mutants. SH-SY5Y cells stably expressing pcDNA3, lipin-1alpha-V5 or lipin-1alpha-K566R/K596R-V5. Cerebrocortical neurons from embryonic day 17 rat embryos transfected either with V5-tagged lipin-1alpha or lipin-1beta, or with the corresponding double sumoylation site mutants
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
both lipin 2 mRNA and protein expression are significantly induced by food deprivation. Lipin 2 knockdown leads to a compensatory increase in Lpin3 mRNA expression, especially in fld hepatocytes
-
hepatic lipin-1 expression is selectively stimulated by glucocorticoids. The expression of lipin-1 is markedly upregulated under stress conditions
-
hepatic lipin-1 expression levels and VLDL secretion both increase in obese individuals following gastric bypass surgery
-
in the 3T3-L1 cell line, lipin-2 protein levels decline dramatically as adipocyte differentiation proceeds to become virtually undetectable in mature adipocytes, when lipin-1 is expressed at high levels
-
lipin 1 knockdown by shRNA, decline in lipin 1 expression with increasing obesity in ob/ob mice
-
lipin 2 protein content is increased in fld liver independent of changes in steady-state Lpin2 mRNA levels. Lipin 2 is dynamically regulated in liver but is not a target gene of peroxisome proliferator-activated receptorgamma-coactivator 1alpha
-
lipin-1 gene expression is regulated in a glucocorticoid receptor-dependent manner
-
lipin-1A and -B expression levels increase dramatically during differentiation of 3T3-L1 preadipocytes to mature adipocytes. Glucocorticoids are the stimulus for the induction of lipin-1 expression in differentiating adipocytes. Lpin1 glucocorticoid response element binds to the glucocorticoid receptor and leads to transcriptional activation in adipocytes and hepatocytes. The Lpin1 promoter directly binds the glucocorticoid receptor in a hormone-dependent manner. Dexamethasone rapidly induces lipin-1 gene expression in a dose-dependent manner, it acts at the level of lipin-1 gene transcription. In response to 0.001 mM dexamethasone treatment, lipin-1B mRNA levels increase as early as 1 h, and lipin-1A levels after 2 h, whereby lipin-1B levels peak with a 7fold induction at 2 h and lipin-1A levels increase to a maximum of 3fold above baseline and remain elevated near this level throughout 24 h. Adipose tissue lipin-1 expression is increased in conditions associated with increased local glucocorticoid concentrations in vivo
-
lipin-2 is most prominently expressed in liver, where levels are much higher than lipin-1, and also in kidney, lung, gastrointestinal tract, and specific regions of the brain. Fasting induces hepatic lipin-1 by 25fold and lipin-2 by 5fold. Lipin-2 is also expressed in circulating red blood cells and sites of lymphopoiesis, like bone marrow, thymus, and spleen
-
RNAi against lipin 2 markedly reduces PAP-1 activity in hepatocytes from both wild-type and fld mice and suppresses triglyceride synthesis under conditions of high fatty acid availability
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
radiolabeled and fluorescent lipid substrates for the detection, quantitation and analysis of the enzymatic activities of the LPPs measured using intact or broken cell preparations as the source of enzyme
medicine
additional information
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
medicine
-
LPP3 acts as an ecto-phosphatase that contributes to the equilibration between FTY720 and FTY720-P in vivo
additional information
-
fibroblasts that overexpress LPP1 enter S-phase at approximately the same time as vector control cells
additional information
-
LPP1 overexpression markedly reduces platelet-derived growth factor-induced activation of p42/p44 mitogen-activated protein kinase. This occurs via a mechanism that involves the LPP1-induced down-regulation of typical protein kinase C isoform(s), which are normally required for platelet-derived growth factor-induced activation of p42/p44 mitogen-activated protein kinase and migration
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhang, Q.X.; Pilquil, C.S.; Dewald, J.; Berthiaume, L.G.; Brindley, D.N.
Identification of structurally important domains of lipid phosphate phosphatase-1: implications for its sites of action
Biochem. J.
345
181-184
2000
Mus musculus
-
Long, J.S.; Yokoyama, K.; Tigyi, G.; Pyne, N.J.; Pyne, S.
Lipid phosphate phosphatase-1 regulates lysophosphatidic acid- and platelet-derived-growth-factor-induced cell migration
Biochem. J.
394
495-500
2006
Mus musculus
Pyne, S.; Long, J.S.; Ktistakis, N.T.; Pyne, N.J.
Lipid phosphate phosphatases and lipid phosphate signalling
Biochem. Soc. Trans.
33
1370-1374
2005
Canis lupus familiaris, Homo sapiens, Mus musculus, Rattus norvegicus
Yue, J.; Yokoyama, K.; Balazs, L.; Baker, D.L.; Smalley, D.; Pilquil, C.; Brindley, D.N.; Tigyi, G.
Mice with transgenic overexpression of lipid phosphate phosphatase-1 display multiple organotypic deficits without alteration in circulating lysophosphatidate level
Cell. Signal.
16
385-399
2004
Mus musculus
Brindley, D.N.
Lipid phosphate phosphatases and related proteins: signaling functions in development, cell division, and cancer
J. Cell. Biochem.
92
900-912
2004
Drosophila melanogaster, Mus musculus, Rattus norvegicus, Homo sapiens (Q6T4P5), Homo sapiens (Q7Z2D5), Homo sapiens (Q8TBJ4), Homo sapiens (Q96GM1)
Pyne, S.; Kong, K.C.; Darroch, P.I.
Lysophosphatidic acid and sphingosine 1-phosphate biology: the role of lipid phosphate phosphatases
Semin. Cell Dev. Biol.
15
491-501
2004
Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Gowri, P.M.; Sengupta, S.; Bertera, S.; Katzenellenbogen, B.S.
Lipin1 regulation by estrogen in uterus and liver: implications for diabetes and fertility
Endocrinology
148
3685-3693
2007
Mus musculus
Mechtcheriakova, D.; Wlachos, A.; Sobanov, J.; Bornancin, F.; Zlabinger, G.; Baumruker, T.; Billich, A.
FTY720-phosphate is dephosphorylated by lipid phosphate phosphatase 3
FEBS Lett.
581
3063-3068
2007
Homo sapiens, Mus musculus
Pilquil, C.; Dewald, J.; Cherney, A.; Gorshkova, I.; Tigyi, G.; English, D.; Natarajan, V.; Brindley, D.N.
Lipid phosphate phosphatase-1 regulates lysophosphatidate-induced fibroblast migration by controlling phospholipase D2-dependent phosphatidate generation
J. Biol. Chem.
281
38418-38429
2006
Mus musculus, Rattus norvegicus
Morris, K.E.; Schang, L.M.; Brindley, D.N.
Lipid phosphate phosphatase-2 activity regulates S-phase entry of the cell cycle in Rat2 fibroblasts
J. Biol. Chem.
281
9297-9306
2006
Homo sapiens, Mus musculus, Rattus norvegicus
Harris, T.E.; Huffman, T.A.; Chi, A.; Shabanowitz, J.; Hunt, D.F.; Kumar, A.; Lawrence, J.C.
Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic acid phosphatase, lipin 1
J. Biol. Chem.
282
277-286
2007
Mus musculus (Q91ZP3)
Donkor, J.; Sariahmetoglu, M.; Dewald, J.; Brindley, D.N.; Reue, K.
Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns
J. Biol. Chem.
282
3450-3457
2007
Saccharomyces cerevisiae, Mus musculus
McDermott, M.I.; Sigal, Y.J.; Crump, J.S.; Morris, A.J.
Enzymatic analysis of lipid phosphate phosphatases
Methods
39
169-179
2006
Homo sapiens, Mus musculus, Rattus norvegicus
Long, J.S.; Pyne, N.J.; Pyne, S.
Lipid phosphate phosphatases form homo- and hetero-oligomers: catalytic competency, subcellular distribution and function
Biochem. J.
411
371-377
2008
Cavia porcellus, Cricetulus griseus, Homo sapiens, Mus musculus
Grkovich, A.; Armando, A.; Quehenberger, O.; Dennis, E.A.
TLR-4 mediated group IVA phospholipase A2 activation is phosphatidic acid phosphohydrolase 1 and protein kinase C dependent
Biochim. Biophys. Acta
1791
975-982
2009
Mus musculus
Ryu, D.; Oh, K.J.; Jo, H.Y.; Hedrick, S.; Kim, Y.N.; Hwang, Y.J.; Park, T.S.; Han, J.S.; Choi, C.S.; Montminy, M.; Koo, S.H.
TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1
Cell Metab.
9
240-251
2009
Mus musculus
Grimsey, N.; Han, G.S.; OHara, L.; Rochford, J.J.; Carman, G.M.; Siniossoglou, S.
Temporal and spatial regulation of the phosphatidate phosphatases lipin 1 and 2
J. Biol. Chem.
283
29166-29174
2008
Mus musculus, Homo sapiens (Q14693)
Carman, G.M.; Han, G.
Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis
J. Biol. Chem.
284
2593-2597
2009
Saccharomyces cerevisiae, Homo sapiens, Mus musculus
Gropler, M.C.; Harris, T.E.; Hall, A.M.; Wolins, N.E.; Gross, R.W.; Han, X.; Chen, Z.; Finck, B.N.
Lipin 2 is a liver-enriched phosphatidate phosphohydrolase enzyme that is dynamically regulated by fasting and obesity in mice
J. Biol. Chem.
284
6763-6772
2009
Mus musculus
Reue, K.; Brindley, D.N.
Thematic Review Series: Glycerolipids. Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism
J. Lipid Res.
49
2493-2503
2008
Saccharomyces cerevisiae, Homo sapiens, Mus musculus, Rattus norvegicus
Brindley, D.N.; Pilquil, C.; Sariahmetoglu, M.; Reue, K.
Phosphatidate degradation: phosphatidate phosphatases (lipins) and lipid phosphate phosphatases
Biochim. Biophys. Acta
1791
956-961
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Pyne, S.; Lee, S.C.; Long, J.; Pyne, N.J.
Role of sphingosine kinases and lipid phosphate phosphatases in regulating spatial sphingosine 1-phosphate signalling in health and disease
Cell. Signal.
21
14-21
2009
Drosophila melanogaster, Homo sapiens, Mus musculus
Koh, Y.K.; Lee, M.Y.; Kim, J.W.; Kim, M.; Moon, J.S.; Lee, Y.J.; Ahn, Y.H.; Kim, K.S.
Lipin1 is a key factor for the maturation and maintenance of adipocytes in the regulatory network with CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma 2
J. Biol. Chem.
283
34896-34906
2008
Mus musculus
Donkor, J.; Zhang, P.; Wong, S.; OLoughlin, L.; Dewald, J.; Kok, B.P.; Brindley, D.N.; Reue, K.
A conserved serine residue is required for the phosphatidate phosphatase activity but not the transcriptional coactivator functions of lipin-1 and lipin-2
J. Biol. Chem.
284
29968-29978
2009
Homo sapiens, Mus musculus, Mus musculus C57/BL6J
Han, G.S.; Carman, G.M.
Characterization of the human LPIN1-encoded phosphatidate phosphatase isoforms
J. Biol. Chem.
285
14628-14638
2010
Mus musculus
Peterfy, M.; Harris, T.E.; Fujita, N.; Reue, K.
Insulin-stimulated interaction with 14-3-3 promotes cytoplasmic localization of lipin-1 in adipocytes
J. Biol. Chem.
285
3857-3864
2010
Mus musculus
Zhang, P.; OLoughlin, L.; Brindley, D.N.; Reue, K.
Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis
J. Lipid Res.
49
1519-1528
2008
Homo sapiens, Mus musculus
Reue, K.; Dwyer, J.R.
Lipin proteins and metabolic homeostasis
J. Lipid Res.
50 Suppl
S109-S114
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Brindley, D.N.; Pilquil, C.
Lipid phosphate phosphatases and signaling
J. Lipid Res.
50 Suppl
S225-S230
2009
Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Humtsoe, J.O.; Liu, M.; Malik, A.B.; Wary, K.K.
Lipid phosphate phosphatase 3 stabilization of beta-catenin induces endothelial cell migration and formation of branching point structures
Mol. Cell. Biol.
30
1593-1606
2010
Homo sapiens, Mus musculus
Kim, H.B.; Kumar, A.; Wang, L.; Liu, G.H.; Keller, S.R.; Lawrence, J.C.; Finck, B.N.; Harris, T.E.
Lipin 1 represses NFATc4 transcriptional activity in adipocytes to inhibit secretion of inflammatory factors
Mol. Cell. Biol.
30
3126-3139
2010
Mus musculus
Liu, G.H.; Gerace, L.
Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells
PLoS ONE
4
e7031
2009
Mus musculus
Siniossoglou, S.
Lipins, lipids and nuclear envelope structure
Traffic
10
1181-1187
2009
Saccharomyces cerevisiae, Mus musculus, Rattus norvegicus
Bou Khalil, M.; Blais, A.; Figeys, D.; Yao, Z.
Lipin - The bridge between hepatic glycerolipid biosynthesis and lipoprotein metabolism
Biochim. Biophys. Acta
1801
1249-1259
2010
Homo sapiens, Mus musculus, Rattus norvegicus
Ren, H.; Federico, L.; Huang, H.; Sunkara, M.; Drennan, T.; Frohman, M.; Smyth, S.; Morris, A.
A phosphatidic acid binding/nuclear localization motif determines lipin1 function in lipid metabolism and adipogenesis
Mol. Biol. Cell
21
3171-3181
2010
Mus musculus
Busnelli, M.; Manzini, S.; Parolini, C.; Escalante-Alcalde, D.; Chiesa, G.
Lipid phosphate phosphatase 3 in vascular pathophysiology
Atherosclerosis
271
156-165
2018
Homo sapiens (O14495), Mus musculus (Q99JY8)
Federico, L.; Yang, L.; Brandon, J.; Panchatcharam, M.; Ren, H.; Mueller, P.; Sunkara, M.; Escalante-Alcalde, D.; Morris, A.J.; Smyth, S.S.
Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice
PLoS ONE
13
e0198063
2018
Mus musculus (Q99JY8)
EXTERNAL LINKS (specific for EC-Number 3.1.3.4)
Transporter Classification Database (TCDB): 9.B.105.3.2
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