Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin.
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Positional cloning identified Lpin1 (encoding lipin) as the fatty liver dystrophy (fld) gene; lipin is a nuclear protein required for normal adipose tissue development.
"The gene (Lpin1) encodes a novel nuclear protein which we have named lipin."
Temporal and spatial regulation of the phosphatidate phosphatases lipin 1 and 2.
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Lipin 1 is the major cellular PAP1 enzyme (siRNA depletion removes ~86% of PAP1 activity); lipin 1 is predominantly cytosolic; PAP1 activity is inhibited by mitotic phosphorylation.
"lipin 1-depleted extracts show an 86% reduction in the total cellular PAP1 activity, indicating that lipin 1 is the major PAP1 enzyme in these cells"
Characterization of the human LPIN1-encoded phosphatidate phosphatase isoforms.
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Purified human lipin 1 alpha/beta/gamma isoforms are Mg2+/Mn2+-dependent PA phosphatases with defined kinetic parameters.
"PA phosphatase activities of the alpha, beta, and gamma isoforms were dependent on Mg(2+) or Mn(2+) ions at pH 7.5 at 37 degrees C."
Cell autonomous lipin 1 function is essential for development and maintenance of white and brown adipose tissue.
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Cell-autonomous lipin 1 is required for WAT and BAT development/maintenance; loss alters PPARalpha/PGC-1alpha/UCP1 expression and cold sensitivity.
"Loss of lipin 1 also affected BAT development and function, as revealed by histological changes, defects in the expression of peroxisome proliferator-activated receptor alpha (PPARalpha), PGC-1alpha, and UCP1, and functionally by altered cold sensitivity."
Phosphorylation of lipin 1 and charge on the phosphatidic acid head group control its phosphatidic acid phosphatase activity and membrane association.
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Lipin 1 is a Mg2+-dependent PA phosphatase whose membrane association and activity are controlled by phosphorylation (mTOR) and PA head-group charge; lipins are soluble proteins that translocate to membranes to act.
"lipins are not integral membrane proteins, and they need to translocate from the cytosol to intracellular membranes to participate in glycerolipid synthesis"
Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate.
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Fatty acids drive KAT5/Tip60-dependent acetylation of lipin 1 and its cytosol-to-ER translocation to generate DAG for TAG synthesis; lipin 1 catalyzes the penultimate step of TAG synthesis.
"the dephosphorylation of phosphatidic acids (PAs) to form diacylglycerols (DAGs), the penultimate step in TAG synthesis"
Lipid signalling drives proteolytic rewiring of mitochondria by YME1L.
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mTORC1-LIPIN1-YME1L axis: LIPIN1 PAP activity decreases mitochondrial phosphatidylethanolamine and promotes YME1L-mediated proteolysis.
"a lipid signalling cascade via the phosphatidic acid phosphatase LIPIN1, which decreases phosphatidylethanolamine levels in mitochondrial membranes"
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
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Large-scale yeast two-hybrid interactome of ~500 neurodegenerative-disease proteins; LPIN1 appears among the mapped interactors. Source of a bare protein-binding IPI annotation, uninformative about lipin-1 function.
"an interactome map that focuses on neurodegenerative disease (ND), connects ~5,000 human proteins via ~30,000 candidate interactions"
The antidepressant drug sertraline is a novel inhibitor of yeast Pah1 and human lipin 1 phosphatidic acid phosphatases.
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Sertraline is a novel noncompetitive inhibitor of PAP, inhibiting the PAP activity of human lipin 1 (alpha, beta, gamma).
"Sertraline also inhibited the PAP activity of human lipin 1"
PA is dephosphorylated to DAG by LPIN
Nuclear Envelope Breakdown
CTDNEP1:CNEP1R1 dephosphorylates LPIN
LPIN catalyzes conversion of phosphatidic acid to diacylglycerol
Triglyceride biosynthesis
1,2-diacyl-glycerol 3-phosphate + H2O => 1,2-diacyl-glycerol + orthophosphate