BRENDA - Enzyme Database

A conserved serine residue is required for the phosphatidate phosphatase activity but not the transcriptional coactivator functions of lipin-1 and lipin-2

Donkor, J.; Zhang, P.; Wong, S.; OLoughlin, L.; Dewald, J.; Kok, B.P.; Brindley, D.N.; Reue, K.; J. Biol. Chem. 284, 29968-29978 (2009)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
3.1.3.4
V5 epitope-tagged lipin-1 and lipin-2 expression plasmids, transiently transfected into Hepa 1–6 cells. Wild-type lipin-1A and lipin-2 and mutants lipin-1A-S724L and lipin-2-S731L expressed in HEK-293 cells
Mus musculus
Engineering
EC Number
Amino acid exchange
Commentary
Organism
3.1.3.4
D679
mutation of the PAP motif, abolishes PAP activity
Mus musculus
3.1.3.4
IL693FF
mutation of the coactivator motif, abolishes PAP activity
Mus musculus
3.1.3.4
S724L
lipin-1 mutant
Mus musculus
3.1.3.4
S731D
PAP deficiency, does not result from impaired membrane association. Exhibits normal membrane localization
Mus musculus
3.1.3.4
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
Mus musculus
3.1.3.4
S734L
Majeed mutation in lipin-2, which alters a serine residue that is located in the C-LIP domain downstream of the enzyme active site and coactivator motifs. Mutation completely abolishes PAP activity in both lipin-1 and lipin-2 backgrounds
Homo sapiens
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
3.1.3.4
cytosol
wild-type and lipin-2 are present at similar levels in cytosolic and membrane fractions in the absence of oleate
Mus musculus
5829
-
3.1.3.4
membrane
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
Mus musculus
16020
-
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.1.3.4
Homo sapiens
-
-
-
3.1.3.4
Mus musculus
-
C57BL/6J mice
-
3.1.3.4
Mus musculus C57/BL6J
-
C57BL/6J mice
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.3.4
blood
lipin-2, in circulating red blood cells, at ca. 10% of the levels observed in liver
Mus musculus
-
3.1.3.4
bone
low levels of lipin-2, in bone and bone marrow, at 10–20% the levels in liver
Mus musculus
-
3.1.3.4
bone marrow
lipin-2
Mus musculus
-
3.1.3.4
brain
lipin-2, in the cortex, hippocampus, thalamus, and hypothalamus
Mus musculus
-
3.1.3.4
duodenum
lipin-2
Mus musculus
-
3.1.3.4
esophagus
lipin-2
Mus musculus
-
3.1.3.4
gastrointestinal tract
lipin-2
Mus musculus
-
3.1.3.4
ileum
lipin-2
Mus musculus
-
3.1.3.4
intestinal mucosa
lipin-2, epithelial cell layer
Mus musculus
-
3.1.3.4
jejunum
lipin-2
Mus musculus
-
3.1.3.4
kidney
lipin-2, in the cortex, medulla, and papillae
Mus musculus
-
3.1.3.4
liver
lipin-2, shows a uniform distribution pattern
Mus musculus
-
3.1.3.4
lung
lipin-2
Mus musculus
-
3.1.3.4
salivary gland
lipin-2, submandibular and submaxillary salivary glands
Mus musculus
-
3.1.3.4
skin
low levels of lipin-1, whereas lipin-2 is absent
Mus musculus
-
3.1.3.4
spleen
lipin-2, in whole spleen and the white blood cell fraction of spleen, at ca. 10% of the levels observed in liver
Mus musculus
-
3.1.3.4
thymus
lipin-2
Mus musculus
-
3.1.3.4
tongue
lipin-2, in squamous keratinized epithelium
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
-
709065
Mus musculus
1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
phosphatidic acid + H2O
-
709065
Mus musculus C57/BL6J
1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
3.1.3.4
V5 epitope-tagged lipin-1 and lipin-2 expression plasmids, transiently transfected into Hepa 1–6 cells. Wild-type lipin-1A and lipin-2 and mutants lipin-1A-S724L and lipin-2-S731L expressed in HEK-293 cells
Mus musculus
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
3.1.3.4
D679
mutation of the PAP motif, abolishes PAP activity
Mus musculus
3.1.3.4
IL693FF
mutation of the coactivator motif, abolishes PAP activity
Mus musculus
3.1.3.4
S724L
lipin-1 mutant
Mus musculus
3.1.3.4
S731D
PAP deficiency, does not result from impaired membrane association. Exhibits normal membrane localization
Mus musculus
3.1.3.4
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
Mus musculus
3.1.3.4
S734L
Majeed mutation in lipin-2, which alters a serine residue that is located in the C-LIP domain downstream of the enzyme active site and coactivator motifs. Mutation completely abolishes PAP activity in both lipin-1 and lipin-2 backgrounds
Homo sapiens
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
3.1.3.4
cytosol
wild-type and lipin-2 are present at similar levels in cytosolic and membrane fractions in the absence of oleate
Mus musculus
5829
-
3.1.3.4
membrane
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
Mus musculus
16020
-
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
3.1.3.4
blood
lipin-2, in circulating red blood cells, at ca. 10% of the levels observed in liver
Mus musculus
-
3.1.3.4
bone
low levels of lipin-2, in bone and bone marrow, at 10–20% the levels in liver
Mus musculus
-
3.1.3.4
bone marrow
lipin-2
Mus musculus
-
3.1.3.4
brain
lipin-2, in the cortex, hippocampus, thalamus, and hypothalamus
Mus musculus
-
3.1.3.4
duodenum
lipin-2
Mus musculus
-
3.1.3.4
esophagus
lipin-2
Mus musculus
-
3.1.3.4
gastrointestinal tract
lipin-2
Mus musculus
-
3.1.3.4
ileum
lipin-2
Mus musculus
-
3.1.3.4
intestinal mucosa
lipin-2, epithelial cell layer
Mus musculus
-
3.1.3.4
jejunum
lipin-2
Mus musculus
-
3.1.3.4
kidney
lipin-2, in the cortex, medulla, and papillae
Mus musculus
-
3.1.3.4
liver
lipin-2, shows a uniform distribution pattern
Mus musculus
-
3.1.3.4
lung
lipin-2
Mus musculus
-
3.1.3.4
salivary gland
lipin-2, submandibular and submaxillary salivary glands
Mus musculus
-
3.1.3.4
skin
low levels of lipin-1, whereas lipin-2 is absent
Mus musculus
-
3.1.3.4
spleen
lipin-2, in whole spleen and the white blood cell fraction of spleen, at ca. 10% of the levels observed in liver
Mus musculus
-
3.1.3.4
thymus
lipin-2
Mus musculus
-
3.1.3.4
tongue
lipin-2, in squamous keratinized epithelium
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
-
709065
Mus musculus
1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
3.1.3.4
phosphatidic acid + H2O
-
709065
Mus musculus C57/BL6J
1,2-diacyl-sn-glycerol + phosphate
-
-
-
?
Expression
EC Number
Organism
Commentary
Expression
3.1.3.4
Mus musculus
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
up
General Information
EC Number
General Information
Commentary
Organism
3.1.3.4
malfunction
symptoms of the Majeed syndrome result from a loss of lipin-2 PAP activity. Loss of lipin-2 PAP activity in erythrocytes and lymphocytes may contribute to the anemia and inflammation phenotypes observed in Majeed syndrome patients
Homo sapiens
3.1.3.4
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
Mus musculus
General Information (protein specific)
EC Number
General Information
Commentary
Organism
3.1.3.4
malfunction
symptoms of the Majeed syndrome result from a loss of lipin-2 PAP activity. Loss of lipin-2 PAP activity in erythrocytes and lymphocytes may contribute to the anemia and inflammation phenotypes observed in Majeed syndrome patients
Homo sapiens
3.1.3.4
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
Mus musculus
Expression (protein specific)
EC Number
Organism
Commentary
Expression
3.1.3.4
Mus musculus
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
up