Any feedback?
Literature summary for 3.1.3.4 extracted from
- Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic acid phosphatase, lipin 1 (2007), J. Biol. Chem., 282, 277-286.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| epinephrine | promotes dephosphorylation of lipin, but has no effect on PAP activity, markedly increases amounts of lipin and PAP activity in microsomes | Mus musculus |  |
| 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 | |
| additional information | fasting increases Mg2+-dependent PAP activity in livers from wild type animals by 2fold | Mus musculus | |
| 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 | Mus musculus | |
| 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
| Application | Comment | Organism |
|---|---|---|
| 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)
| Cloned (Comment) | Organism |
|---|---|
| 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 |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| G84R | PAP activity is ca. 20% that of the wild-type enzyme | Mus musculus |
| G84R | site-directed mutagenesis, the mutant shows a 80% reduced activity compared to the wild-type lipin 1 | Mus musculus |
| 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 | Mus musculus |
| 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 | Mus musculus |
| S106A | increases electrophoretic mobility of lipin but abolishes the shift in electrophoretic mobility produced by insulin | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 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 | |
| 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 | |
| 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 | |
| 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
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | the less phosphorylated enzyme forms are located in the cytosol | Mus musculus | 5829 | - |
| membrane | - |
Mus musculus | 16020 | - |
| membrane | the more phosphorylated enzyme forms are associated to membranes | Mus musculus | 16020 | - |
| microsome | - |
Mus musculus | - |
- |
| soluble | - |
Mus musculus | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Mus musculus | |
| Mg2+ | dependent on | Mus musculus | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 30000 | - |
NH2-terminal region, including the conserved NLIP domain present, immunoprecipitation | Mus musculus |
| 45000 | - |
conserved CLIP domain present, immunoprecipitation | Mus musculus |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 1,2-dioleoyl-sn-glycerol-3 phosphate | 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
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mus musculus | Q91ZP3 | - |
- |
| Mus musculus | Q91ZP3 | heterozygous BALB/cByJ-fld/+ mice | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | identification of fifteen phosphorylation sites by mass spectrometric analysis | Mus musculus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| 3T3-L1 cell | - |
Mus musculus | - |
| adipocyte | - |
Mus musculus | - |
| brain | - |
Mus musculus | - |
| brain | fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice | Mus musculus | - |
| heart | - |
Mus musculus | - |
| heart | fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice | Mus musculus | - |
| kidney | - |
Mus musculus | - |
| kidney | fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice | Mus musculus | - |
| liver | - |
Mus musculus | - |
| liver | fatty liver dystrophy | Mus musculus | - |
| liver | Mg2+-dependent PAP activity from fatty liver dystrophy mice is approximately half of that measured in wild-type | Mus musculus | - |
| lung | fatty liver dystrophy mice contain dramatically lower levels of Mg2+-dependent PAP activity than wild-type mice | Mus musculus | - |
| skeletal muscle | - |
Mus musculus | - |
| 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)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 1,2-dioleoyl-sn-glycerol-3 phosphate | - |
Mus musculus | 1,2-dioleoyl-sn-glycerol + phosphate | - |
? | |
| 1,2-dioleoyl-sn-glycerol-3 phosphate | insulin and epinephrine control lipin 1 primarily by changing localization rather than intrinsic PAP activity, overview | Mus musculus | 1,2-dioleoyl-sn-glycerol + phosphate | - |
? | |
| phosphatidic acid + H2O | - |
Mus musculus | phosphate + diacylglycerol | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| lipin 1 | - |
Mus musculus |
| Mg2+-dependent phosphatidic acid phosphatase | - |
Mus musculus |
| PAP | - |
Mus musculus |
| phosphatidic acid phosphatase | - |
Mus musculus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Mus musculus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7 | - |
assay at | Mus musculus |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
