Gene Ontology annotation through association of InterPro records with GO terms
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
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase.
Apolipoprotein C-II39-62 activates lipoprotein lipase by direct lipid-independent binding.
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APOC2 activates LPL through a direct interaction with the loop covering the LPL active site in this assay system.
"We suggest that while the binding of apoC-II to the lipid surface promotes the formation of a high-affinity complex of apoC-II and LpL, activation occurs via direct helix-helix interactions between apoC-II39-62 and the loop covering the active site of LpL."
Heparin-binding defective lipoprotein lipase is unstable and causes abnormalities in lipid delivery to tissues.
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Mutation of three C-terminal basic residues produced catalytically active human LPL with reduced heparin binding.
"Three basic amino acids in the carboxyl terminal region of LpL were mutated, yielding an active enzyme with reduced heparin binding."
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HSPG/heparin association stabilizes LPL and contributes to normal tissue targeting of lipids in vivo.
"Thus, heparin association is required for LpL stability and normal physiologic functions."
Structural and functional consequences of missense mutations in exon 5 of the lipoprotein lipase gene.
Characterization of the lipolytic activity of endothelial lipase.
VLDL-induced triglyceride accumulation in human macrophages is mediated by modulation of LPL lipolytic activity in the absence of change in LPL mass.
Novel LPL mutation (L303F) found in a patient associated with coronary artery disease and severe systemic atherosclerosis.
Human lipoprotein lipase. Analysis of the catalytic triad by site-directed mutagenesis of Ser-132, Asp-156, and His-241.
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Human LPL hydrolyzes triglycerides in chylomicrons and VLDL.
"Lipoprotein lipase (LPL) plays a central role in normal lipid metabolism as the key enzyme involved in the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins."
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Ser132, Asp156, and His241 form the human LPL catalytic triad.
"These combined results strongly support the conclusion that Ser-132, Asp-156, and His-241 form the catalytic triad of LPL and are essential for LPL hydrolytic activity."
Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5.
Calcium triggers folding of lipoprotein lipase into active dimers.
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Calcium promotes folding of LPL monomers into a dimerization-competent state that rapidly forms active dimers in this biochemical system.
"The second step was promoted by Ca2+ and converted LPL monomers from the molten globule state to dimerization-competent and more tightly folded monomers that rapidly formed active LPL dimers."
Human colostrum: identification of minor proteins in the aqueous phase by proteomics.
Reduction of plasma triglycerides in apolipoprotein C-II transgenic mice overexpressing lipoprotein lipase in muscle.
Effect of serum and C-apoproteins from very low density lipoproteins on human postheparin plasma hepatic lipase.
GPIHBP1 stabilizes lipoprotein lipase and prevents its inhibition by angiopoietin-like 3 and angiopoietin-like 4.
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GPIHBP1 stabilized LPL without directly activating it.
"Like heparin, GPIHBP1 stabilized but did not activate LPL."
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Under the tested conditions, GPIHBP1-bound LPL resisted ANGPTL4 inhibition.
"ANGPTL4 potently inhibited nonstabilized LPL as well as heparin-stabilized LPL but not GPIHBP1-stabilized LPL."
Missense mutation (Gly→Glu188) of human lipoprotein lipase imparting functional deficiency.
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Human LPL Gly188Glu was catalytically inactive and had reduced heparin affinity in vitro.
"By contrast, the mutant enzyme expressed in vitro was catalytically inactive and displayed a lower affinity for heparin than the normal enzyme."
Chylomicronemia with low postheparin lipoprotein lipase levels in the setting of GPIHBP1 defects.
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The human GPIHBP1-C65Y variant reaches the cell surface but fails to bind LPL.
"Studies with transfected Chinese hamster ovary cells showed that GPIHBP1-C65Y reaches the cell surface but has lost the ability to bind lipoprotein lipase (LPL)."
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Human GPIHBP1 loss-of-function variants reduce postheparin plasma LPL, linking endothelial LPL capture to human triglyceride metabolism.
"We also show that homozygosity for the C65Y or Q115P mutations is associated with low levels of LPL in the postheparin plasma, demonstrating that GPIHBP1 is important for plasma triglyceride metabolism in humans."
Lipoprotein lipaseBethesda: a single amino acid substitution (Ala-176→Thr) leads to abnormal heparin binding and loss of enzymic activity.
SorLA regulates the activity of lipoprotein lipase by intracellular trafficking.
Rapid and simple isolation procedure for lipoprotein lipase from human milk.
Molecular analysis of chylomicronemia in a clinical laboratory setting: diagnosis of 13 cases of lipoprotein lipase deficiency.
MicroRNA-27a/b regulates cellular cholesterol efflux, influx and esterification/hydrolysis in THP-1 macrophages.
MicroRNA-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting lipoprotein lipase gene in human THP-1 macrophages.
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Lowering LPL through miR-590 reduced pro-inflammatory cytokine secretion in human THP-1 macrophages.
"We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA."
The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain.
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The acidic domain of GPIHBP1 stabilizes LPL catalytic activity by limiting unfolding of its catalytic domain.
"Importantly, the acidic domain stabilizes LPL catalytic activity by mitigating the global unfolding of LPL's catalytic domain."
Identification and characterization of two novel mutations in the LPL gene causing type I hyperlipoproteinemia.
MiR-27b Impairs Adipocyte Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting LPL.
A disordered acidic domain in GPIHBP1 harboring a sulfated tyrosine regulates lipoprotein lipase.
Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis.
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The GPIHBP1 LU domain binds the C-terminal domain of LPL mainly through hydrophobic interactions.
"GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interactions."
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The GPIHBP1 acidic domain is positioned to stabilize LPL by engaging a basic surface spanning both LPL domains.
"GPIHBP1's acidic domain was not defined in the electron density map but was positioned to interact with LPL's large basic patch, providing a likely explanation for how GPIHBP1 stabilizes LPL."
MicroRNA-138 Suppresses Adipogenic Differentiation in Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting Lipoprotein Lipase.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III.
Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I).
Human hepatic and lipoprotein lipase: the loop covering the catalytic site mediates lipase substrate specificity.
chylomicron => TG-depleted chylomicron + 50 long-chain fatty acids + 50 diacylglycerols
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Reactome models endothelial LPL hydrolysis of chylomicron triglycerides to form a triglyceride-depleted remnant.
"The LPL enzyme catalyzes the hydrolysis and release of triacylglycerols (TG) associated with circulating chylomicrons to leave a CM remnant (CR)."
LPL hydrolyses TGs from mature CMs
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Reactome models chylomicron triglyceride hydrolysis by endothelial LPL.
"The LPL enzyme catalyzes the hydrolysis and release of triacylglycerols (TG) associated with circulating chylomicrons to leave a CM remnant (CR)."
Expression of Lipoprotein lipase (LPL)
PCSK6,FURIN mediate dissociation of 2 x LPL from GPIHBP1:HSPG:LPL dimer
PCSK5 mediates dissociation of 2 x LPL from GPIHBP1:HSPG:LPL dimer
HSPG binds LPL dimer
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Reactome models HSPG anchoring of adipocyte-derived LPL at capillary endothelium.
"It is synthesised in adipocytes and exported to the luminal side of the capillary endothelium where it binds heparan sulfate proteoglycan (HSPG), serving as an membrane anchor for the LPL dimer (Lookene et al. 1997, Berryman & Bensadoun 1995)."
GPIHBP1 binds HSPG:LPL dimer
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Reactome models GPIHBP1 transport of interstitial LPL across endothelial cells to the capillary lumen.
"Once bound, GPIHBP1 transports LPL from within interstitial spaces, across endothelial cells to the capillary lumen (Gin et al. 2007, Young et al. 2011, Adeyo et al. 2012)."
GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries.
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LPL is secreted by myocytes and adipocytes and acts within the capillary lumen.
"LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides."
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GPIHBP1 transports LPL across capillary endothelial cells.
"Also, we show that GPIHBP1 is located at the basolateral surface of capillary endothelial cells and actively transports LPL across endothelial cells."
The GPIHBP1-LPL complex is responsible for the margination of triglyceride-rich lipoproteins in capillaries.
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GPIHBP1-bound LPL is required for triglyceride-rich lipoprotein margination at capillaries.
"Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1."
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HSPG-bound LPL was insufficient to restore TRL margination without GPIHBP1.
"Notably, the expression of LPL by endothelial cells in Gpihbp1⁻/⁻ mice did not restore defective TRL margination, implying that the binding of LPL to HSPGs is ineffective in promoting TRL margination."
Mobility of "HSPG-bound" LPL explains how LPL is able to reach GPIHBP1 on capillaries.
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Interstitial HSPG-bound LPL remains mobile and can transfer to endothelial GPIHBP1.
"We conclude that HSPG-bound LPL in the interstitial spaces of tissues is mobile, allowing the LPL to move to GPIHBP1 on endothelial cells."
The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding.
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ANGPTL4 inactivates LPL by catalyzing unfolding of its hydrolase domain.
"We now show: (1) that ANGPTL4 inactivates LPL by catalyzing the unfolding of its hydrolase domain; (2) that binding to GPIHBP1 renders LPL largely refractory to this inhibition; and (3) that both the LU domain and the intrinsically disordered acidic domain of GPIHBP1 are required for this protective effect."
Angiopoietin-like protein 3 inhibits lipoprotein lipase activity through enhancing its cleavage by proprotein convertases.
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In cell-based assays, ANGPTL3 enhanced proprotein-convertase cleavage of LPL and thereby inhibited catalytic and noncatalytic functions.
"By enhancing LPL cleavage, ANGPTL3 dissociates LPL from the cell surface, inhibiting both the catalytic and noncatalytic functions of LPL."
Site-directed mutagenesis of apolipoprotein CII to probe the role of its secondary structure for activation of lipoprotein lipase.
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APOC2 C-terminal helical structure is important for LPL activation, while the previously proposed 39-62 fragment was inactive in this study.
"Finally, fragment 39-62, previously claimed to activate LPL, was found to be completely inactive."
Purification, cellular levels, and functional domains of lipase maturation factor 1.
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ER-resident LMF1 is required for LPL secretion and enzymatic activity.
"LPL requires an endoplasmic reticulum (ER)-resident, transmembrane protein known as lipase maturation factor 1 (LMF1) for secretion and enzymatic activity."
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All tested LMF1 domains were necessary for LPL maturation.
"N-terminal truncations of LMF1 show that all the domains are necessary for LPL maturation."
ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride clearance.
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ANGPTL8 required ANGPTL3 to inhibit LPL and raise plasma triglycerides in the mouse experiments.
"Collectively, these data show that ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in mice in the presence of ANGPTL3."