LPL is the principal extracellular lipase that hydrolyzes triacylglycerol in circulating chylomicrons and very-low-density lipoproteins, releasing fatty acids for tissue uptake and converting the particles into remodeled remnants. It is synthesized and secreted chiefly by parenchymal cells such as myocytes and adipocytes, captured from the interstitial space by the endothelial protein GPIHBP1, transported across capillary endothelial cells, and presented on the luminal surface. GPIHBP1-bound LPL also promotes margination of triglyceride-rich lipoproteins at capillaries and stabilizes the enzyme against unfolding. APOC2 on lipoprotein particles activates LPL, whereas ANGPTL-family proteins inhibit LPL in tissue- and nutritional-state-dependent contexts. Heparan sulfate proteoglycan binding contributes to interstitial retention, mobility, stability, and transfer of LPL to GPIHBP1. LPL uses a serine-aspartate-histidine catalytic triad and has a secondary, lower glycerophospholipid phospholipase A1 activity. The translated precursor contains a cleavable N-terminal signal peptide; residues 28-475 form the mature secreted enzyme, with no separate regulatory propeptide. ER-resident LMF1 is required for productive LPL maturation and secretion but is not part of the extracellular catalytic assembly. LPL can form homodimers in biochemical preparations, while structural and biochemical evidence also supports active GPIHBP1-stabilized monomeric LPL, so dimerization is not an invariant requirement. Biallelic loss of LPL catalytic function causes familial chylomicronemia with severe hypertriglyceridemia; inflammatory, adipogenic, and storage phenotypes are downstream, context-dependent consequences of altered lipid delivery rather than additional core molecular activities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Propagation Review Root cause: NO FAILURE CORE Sources checked: FB:FBgn0004047 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. MGI:MGI:96216 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. MGI:MGI:96820 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. PANTHER:PTN008325466 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. RGD:1310740 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. RGD:3009 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. RGD:3017 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. RGD:3360 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. RGD:620792 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. RGD:620793 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. RGD:621261 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:P06858 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:P11150 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:P16233 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:P54317 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:Q6XZB0 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:Q8WWY8 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:Q9Y5X9 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0019433 triglyceride catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:96820 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. PANTHER:PTN000906454 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. UniProtKB:D7EZN2 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. UniProtKB:P06858 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. UniProtKB:P11150 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. UniProtKB:P54317 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0006633 fatty acid biosynthetic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Fatty-acid biosynthesis is downstream of, rather than catalyzed by, LPL. Reason: LPL hydrolyzes lipoprotein triacylglycerol and releases fatty acids. Those products can be re-esterified or used in biosynthesis, but LPL does not catalyze fatty-acid synthesis; this process assignment conflates substrate delivery with the biosynthetic pathway. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000906454 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it does not establish the overextended fatty acid biosynthetic process assignment for human LPL. UniProtKB:P06858 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it does not establish the overextended fatty acid biosynthetic process assignment for human LPL. UniProtKB:P11150 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it does not establish the overextended fatty acid biosynthetic process assignment for human LPL. UniProtKB:P11151 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it does not establish the overextended fatty acid biosynthetic process assignment for human LPL. |
| GO:0008970 glycerophospholipid phospholipase A1 activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retained as a secondary, non-core phospholipase activity of LPL. Reason: LPL has experimentally supported glycerophospholipid phospholipase A1 activity, but it is low relative to its defining lipoprotein triacylglycerol lipase activity and its physiological contribution remains uncertain. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000906454 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed glycerophospholipid phospholipase A1 activity assignment for human LPL. RGD:3009 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed glycerophospholipid phospholipase A1 activity assignment for human LPL. UniProtKB:P06858 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed glycerophospholipid phospholipase A1 activity assignment for human LPL. UniProtKB:P11150 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed glycerophospholipid phospholipase A1 activity assignment for human LPL. UniProtKB:Q9Y5X9 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed glycerophospholipid phospholipase A1 activity assignment for human LPL. |
| GO:0034375 high-density lipoprotein particle remodeling | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: HDL-particle remodeling is an overextended lipase-family transfer for LPL. Reason: LPL has low but detectable phospholipase activity, but the available LPL-specific evidence does not directly establish HDL remodeling as an in-vivo LPL process. The IBA is driven by a broad lipase node and endothelial/hepatic lipase sources, whose HDL-remodeling roles should not be transferred unqualified to LPL. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000906454 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it supports lipase-family or paralog HDL biology but does not directly establish HDL remodeling by human LPL. RGD:3009 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it supports lipase-family or paralog HDL biology but does not directly establish HDL remodeling by human LPL. UniProtKB:P11150 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it supports lipase-family or paralog HDL biology but does not directly establish HDL remodeling by human LPL. UniProtKB:Q9Y5X9 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it supports lipase-family or paralog HDL biology but does not directly establish HDL remodeling by human LPL. |
| GO:0042632 cholesterol homeostasis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retained as non-core: Cholesterol homeostasis is a systemic consequence of lipoprotein remodeling and clearance rather than the defining LPL reaction. Reason: Cholesterol homeostasis is a systemic consequence of lipoprotein remodeling and clearance rather than the defining LPL reaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:96216 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cholesterol homeostasis assignment for human LPL. PANTHER:PTN000906454 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cholesterol homeostasis assignment for human LPL. UniProtKB:P06858 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cholesterol homeostasis assignment for human LPL. UniProtKB:P11150 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cholesterol homeostasis assignment for human LPL. UniProtKB:Q9Y5X9 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cholesterol homeostasis assignment for human LPL. |
| GO:0034372 very-low-density lipoprotein particle remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted: VLDL remodeling directly reflects hydrolysis of VLDL triacylglycerol by extracellular LPL. Reason: VLDL remodeling directly reflects hydrolysis of VLDL triacylglycerol by extracellular LPL. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002614072 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed very-low-density lipoprotein particle remodeling assignment for human LPL. UniProtKB:P06858 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed very-low-density lipoprotein particle remodeling assignment for human LPL. UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed very-low-density lipoprotein particle remodeling assignment for human LPL. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0004465 lipoprotein lipase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:96820 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. PANTHER:PTN000906454 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. RGD:3017 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. UniProtKB:P06858 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0034185 apolipoprotein binding | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted: Apolipoprotein binding is informative for LPL activation and lipoprotein-particle recognition, including APOC2-dependent catalysis. Reason: Apolipoprotein binding is informative for LPL activation and lipoprotein-particle recognition, including APOC2-dependent catalysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002614072 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed apolipoprotein binding assignment for human LPL. UniProtKB:P06858 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed apolipoprotein binding assignment for human LPL. UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed apolipoprotein binding assignment for human LPL. Supporting Evidence: PMID:10727238 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. |
| GO:0004465 lipoprotein lipase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00088463 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. InterPro:IPR002330 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. EC:3.1.1.34 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027128 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. UniProtKB-SubCell:SL-0243 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed extracellular region assignment for human LPL. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Accepted: LPL acts at the plasma-membrane-facing endothelial surface through GPIHBP1 and proteoglycan interactions. Reason: LPL acts at the plasma-membrane-facing endothelial surface through GPIHBP1 and proteoglycan interactions. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed plasma membrane assignment for human LPL. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: Accepted: Lipid metabolism is broad but correct for the defining extracellular lipolytic activity of LPL. Reason: Lipid metabolism is broad but correct for the defining extracellular lipolytic activity of LPL. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR002330 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipid metabolic process assignment for human LPL. InterPro:IPR016272 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipid metabolic process assignment for human LPL. InterPro:IPR033906 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipid metabolic process assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0006641 triglyceride metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Accepted: Triglyceride metabolism is a valid broader process encompassing LPL-mediated extracellular hydrolysis. Reason: Triglyceride metabolism is a valid broader process encompassing LPL-mediated extracellular hydrolysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028707 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride metabolic process assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0008970 glycerophospholipid phospholipase A1 activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retained as a secondary, non-core phospholipase activity of LPL. Reason: LPL has experimentally supported glycerophospholipid phospholipase A1 activity, but it is low relative to its defining lipoprotein triacylglycerol lipase activity and its physiological contribution remains uncertain. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:18689 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed glycerophospholipid phospholipase A1 activity assignment for human LPL. EC:3.1.1.32 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed glycerophospholipid phospholipase A1 activity assignment for human LPL. |
| GO:0016042 lipid catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Accepted: Lipid catabolism is broad but correct for LPL-mediated triacylglycerol hydrolysis. Reason: Lipid catabolism is broad but correct for LPL-mediated triacylglycerol hydrolysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00028909 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipid catabolic process assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0016298 lipase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Accepted: Lipase activity is a correct parent molecular function for LPL. Reason: Lipase activity is a correct parent molecular function for LPL. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000734 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipase activity assignment for human LPL. InterPro:IPR013818 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipase activity assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0052689 carboxylic ester hydrolase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Accepted: Carboxylic-ester hydrolase activity is a correct broad catalytic parent of LPL lipase activity. Reason: Carboxylic-ester hydrolase activity is a correct broad catalytic parent of LPL lipase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR016272 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed carboxylic ester hydrolase activity assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0005515 protein binding | IPI PMID:20124439 Chylomicronemia with low postheparin lipoprotein lipase leve... | MODIFY | Summary: Modified from generic protein binding to protein-membrane adaptor activity. Reason: The source establishes LPL association with cell-surface GPIHBP1, while independent experiments show that GPIHBP1-bound LPL captures triglyceride-rich particles at capillaries. GO:0043495 describes this functional bridge more informatively than generic protein binding; it does not imply a permanently stable complex. Proposed replacements: protein-membrane adaptor activity Supporting Evidence: PMID:20124439 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). PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0005515 protein binding | IPI PMID:20124439 Chylomicronemia with low postheparin lipoprotein lipase leve... | MODIFY | Summary: Modified from generic protein binding to protein-membrane adaptor activity. Reason: The source establishes LPL association with cell-surface GPIHBP1, while independent experiments show that GPIHBP1-bound LPL captures triglyceride-rich particles at capillaries. GO:0043495 describes this functional bridge more informatively than generic protein binding; it does not imply a permanently stable complex. Proposed replacements: protein-membrane adaptor activity Supporting Evidence: PMID:20124439 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). PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0005515 protein binding | IPI PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | MODIFY | Summary: Modified from generic protein binding to protein-membrane adaptor activity. Reason: The source establishes LPL association with cell-surface GPIHBP1, while independent experiments show that GPIHBP1-bound LPL captures triglyceride-rich particles at capillaries. GO:0043495 describes this functional bridge more informatively than generic protein binding; it does not imply a permanently stable complex. Proposed replacements: protein-membrane adaptor activity Supporting Evidence: PMID:30559189 GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interactions. PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0005515 protein binding | IPI PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | MODIFY | Summary: Modified from generic protein binding to protein-membrane adaptor activity. Reason: The source establishes LPL association with cell-surface GPIHBP1, while independent experiments show that GPIHBP1-bound LPL captures triglyceride-rich particles at capillaries. GO:0043495 describes this functional bridge more informatively than generic protein binding; it does not imply a permanently stable complex. Proposed replacements: protein-membrane adaptor activity Supporting Evidence: PMID:30559189 GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interactions. PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is uninformative for LPL. Reason: The IPI assertion preserves an observed interaction, but GO:0005515 does not describe whether the partner supports secretion, endothelial transport, lipoprotein recognition, catalysis, or an incidental screen hit. It should not represent LPL function without a more informative interaction term. |
| GO:0001523 retinoid metabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: Retinoid handling is a substrate/context-dependent consequence of extracellular lipolysis rather than the defining LPL reaction. Reason: Retinoid handling is a substrate/context-dependent consequence of extracellular lipolysis rather than the defining LPL reaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed retinoid metabolic process assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed retinoid metabolic process assignment for human LPL. |
| GO:0004806 triacylglycerol lipase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triacylglycerol lipase activity assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triacylglycerol lipase activity assignment for human LPL. RHEA:12044 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triacylglycerol lipase activity assignment for human LPL. RHEA:38575 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triacylglycerol lipase activity assignment for human LPL. RHEA:40475 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triacylglycerol lipase activity assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0009986 cell surface | IEA GO_REF:0000107 | ACCEPT | Summary: Accepted: Cell-surface localization is appropriate for extracellular LPL presented at the luminal endothelial surface. Reason: Cell-surface localization is appropriate for extracellular LPL presented at the luminal endothelial surface. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cell surface assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cell surface assignment for human LPL. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0010744 positive regulation of macrophage derived foam cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: Foam-cell differentiation is a macrophage-context phenotype downstream of lipid uptake, not the core LPL catalytic activity. Reason: Foam-cell differentiation is a macrophage-context phenotype downstream of lipid uptake, not the core LPL catalytic activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of macrophage derived foam cell differentiation assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of macrophage derived foam cell differentiation assignment for human LPL. |
| GO:0019433 triglyceride catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0031670 cellular response to nutrient | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: Nutrient response is a broad regulatory context downstream of LPL-dependent lipid delivery. Reason: Nutrient response is a broad regulatory context downstream of LPL-dependent lipid delivery. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cellular response to nutrient assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cellular response to nutrient assignment for human LPL. |
| GO:0032731 positive regulation of interleukin-1 beta production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: Interleukin-1 beta production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Reason: Interleukin-1 beta production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of interleukin-1 beta production assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of interleukin-1 beta production assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: Interleukin-6 production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Reason: Interleukin-6 production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of interleukin-6 production assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of interleukin-6 production assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: Tumor-necrosis-factor production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Reason: Tumor-necrosis-factor production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of tumor necrosis factor production assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of tumor necrosis factor production assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0034447 very-low-density lipoprotein particle clearance | IEA GO_REF:0000107 | ACCEPT | Summary: Accepted: VLDL-particle clearance is a direct physiological consequence of LPL catalysis and receptor/proteoglycan bridging. Reason: VLDL-particle clearance is a direct physiological consequence of LPL catalysis and receptor/proteoglycan bridging. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed very-low-density lipoprotein particle clearance assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed very-low-density lipoprotein particle clearance assignment for human LPL. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0050729 positive regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: Inflammatory-response regulation is a context-dependent downstream role rather than direct LPL catalysis. Reason: Inflammatory-response regulation is a context-dependent downstream role rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of inflammatory response assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of inflammatory response assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0071398 cellular response to fatty acid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: Fatty-acid response is downstream of the fatty acids released by LPL and is not the defining molecular activity. Reason: Fatty-acid response is downstream of the fatty acids released by LPL and is not the defining molecular activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cellular response to fatty acid assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cellular response to fatty acid assignment for human LPL. |
| GO:2000343 positive regulation of chemokine (C-X-C motif) ligand 2 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retained as non-core: CXCL2 regulation is a context-dependent inflammatory output rather than direct LPL catalysis. Reason: CXCL2 regulation is a context-dependent inflammatory output rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of chemokine (C-X-C motif) ligand 2 production assignment for human LPL. ensembl:ENSMUSP00000015712 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of chemokine (C-X-C motif) ligand 2 production assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0006641 triglyceride metabolic process | IMP PMID:12573449 VLDL-induced triglyceride accumulation in human macrophages ... | ACCEPT | Summary: Accepted: Triglyceride metabolism is a valid broader process encompassing LPL-mediated extracellular hydrolysis. Reason: Triglyceride metabolism is a valid broader process encompassing LPL-mediated extracellular hydrolysis. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0010744 positive regulation of macrophage derived foam cell differentiation | IMP PMID:12573449 VLDL-induced triglyceride accumulation in human macrophages ... | KEEP AS NON CORE | Summary: Retained as non-core: Foam-cell differentiation is a macrophage-context phenotype downstream of lipid uptake, not the core LPL catalytic activity. Reason: Foam-cell differentiation is a macrophage-context phenotype downstream of lipid uptake, not the core LPL catalytic activity. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0034372 very-low-density lipoprotein particle remodeling | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted: VLDL remodeling directly reflects hydrolysis of VLDL triacylglycerol by extracellular LPL. Reason: VLDL remodeling directly reflects hydrolysis of VLDL triacylglycerol by extracellular LPL. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed very-low-density lipoprotein particle remodeling assignment for human LPL. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0034372 very-low-density lipoprotein particle remodeling | IMP PMID:12573449 VLDL-induced triglyceride accumulation in human macrophages ... | ACCEPT | Summary: Accepted: VLDL remodeling directly reflects hydrolysis of VLDL triacylglycerol by extracellular LPL. Reason: VLDL remodeling directly reflects hydrolysis of VLDL triacylglycerol by extracellular LPL. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:1905885 positive regulation of triglyceride transport | IMP PMID:12573449 VLDL-induced triglyceride accumulation in human macrophages ... | KEEP AS NON CORE | Summary: Retained as non-core: Triglyceride transport is a physiological consequence of lipoprotein processing and is retained as non-core. Reason: Triglyceride transport is a physiological consequence of lipoprotein processing and is retained as non-core. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0005515 protein binding | IPI PMID:7417307 Activation of human post heparin lipoprotein lipase by apoli... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is uninformative for LPL. Reason: The IPI assertion preserves an observed interaction, but GO:0005515 does not describe whether the partner supports secretion, endothelial transport, lipoprotein recognition, catalysis, or an incidental screen hit. It should not represent LPL function without a more informative interaction term. |
| GO:0050729 positive regulation of inflammatory response | IMP PMID:25149060 MicroRNA-590 attenuates lipid accumulation and pro-inflammat... | KEEP AS NON CORE | Summary: Retained as non-core: Inflammatory-response regulation is a context-dependent downstream role rather than direct LPL catalysis. Reason: Inflammatory-response regulation is a context-dependent downstream role rather than direct LPL catalysis. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0005515 protein binding | IPI PMID:19542565 GPIHBP1 stabilizes lipoprotein lipase and prevents its inhib... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is uninformative for LPL. Reason: The IPI assertion preserves an observed interaction, but GO:0005515 does not describe whether the partner supports secretion, endothelial transport, lipoprotein recognition, catalysis, or an incidental screen hit. It should not represent LPL function without a more informative interaction term. |
| GO:0034447 very-low-density lipoprotein particle clearance | ISS PMID:15178420 Mechanism of triglyceride lowering in mice expressing human ... | ACCEPT | Summary: Accepted: VLDL-particle clearance is a direct physiological consequence of LPL catalysis and receptor/proteoglycan bridging. Reason: VLDL-particle clearance is a direct physiological consequence of LPL catalysis and receptor/proteoglycan bridging. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed very-low-density lipoprotein particle clearance assignment for human LPL. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:11893776 Structural and functional consequences of missense mutations... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:1371284 Human lipoprotein lipase. Analysis of the catalytic triad by... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:16179346 Calcium triggers folding of lipoprotein lipase into active d... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:2340307 Rapid and simple isolation procedure for lipoprotein lipase ... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:26725083 The acidic domain of the endothelial membrane protein GPIHBP... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:27578112 Identification and characterization of two novel mutations i... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:29899144 A disordered acidic domain in GPIHBP1 harboring a sulfated t... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | EXP PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0005576 extracellular region | EXP PMID:11893776 Structural and functional consequences of missense mutations... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | EXP PMID:12641539 Novel LPL mutation (L303F) found in a patient associated wit... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | EXP PMID:1371284 Human lipoprotein lipase. Analysis of the catalytic triad by... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | EXP PMID:24291057 Molecular analysis of chylomicronemia in a clinical laborato... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted: LPL acts at the plasma-membrane-facing endothelial surface through GPIHBP1 and proteoglycan interactions. Reason: LPL acts at the plasma-membrane-facing endothelial surface through GPIHBP1 and proteoglycan interactions. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed plasma membrane assignment for human LPL. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0019433 triglyceride catabolic process | IDA PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0070328 triglyceride homeostasis | NAS PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | KEEP AS NON CORE | Summary: Retained as non-core: Triglyceride homeostasis is a physiological outcome of LPL catalysis and paralog/cofactor context, retained as non-core rather than as an activity definition. Reason: Triglyceride homeostasis is a physiological outcome of LPL catalysis and paralog/cofactor context, retained as non-core rather than as an activity definition. |
| GO:1902494 catalytic complex | IPI PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | MARK AS OVER ANNOTATED | Summary: The generic catalytic-complex annotation is too vague to identify an LPL assembly. Reason: The structure paper supports association of LPL with its endothelial transporter/cofactor GPIHBP1, but GO:1902494 does not specify that assembly and risks implying a constitutive catalytic complex. The interaction is better retained through the source-specific evidence rather than as a generic complex core function. |
| GO:0045600 positive regulation of fat cell differentiation | IMP PMID:31769250 MicroRNA-138 Suppresses Adipogenic Differentiation in Human ... | KEEP AS NON CORE | Summary: Retained as non-core: Adipocyte differentiation is a developmental consequence of lipid delivery and signaling, not the core extracellular lipase reaction. Reason: Adipocyte differentiation is a developmental consequence of lipid delivery and signaling, not the core extracellular lipase reaction. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:1904179 positive regulation of adipose tissue development | IMP PMID:31769250 MicroRNA-138 Suppresses Adipogenic Differentiation in Human ... | KEEP AS NON CORE | Summary: Retained as non-core: Adipose-tissue development is a downstream organismal phenotype and is retained as non-core. Reason: Adipose-tissue development is a downstream organismal phenotype and is retained as non-core. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0010884 positive regulation of lipid storage | TAS PMID:24608080 MicroRNA-27a/b regulates cellular cholesterol efflux, influx... | KEEP AS NON CORE | Summary: Retained as non-core: Lipid storage is downstream of uptake and re-esterification of LPL-released fatty acids. Reason: Lipid storage is downstream of uptake and re-esterification of LPL-released fatty acids. |
| GO:0004806 triacylglycerol lipase activity | IDA PMID:12032167 Characterization of the lipolytic activity of endothelial li... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | IDA PMID:7592706 Human hepatic and lipoprotein lipase: the loop covering the ... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0008970 glycerophospholipid phospholipase A1 activity | IDA PMID:12032167 Characterization of the lipolytic activity of endothelial li... | KEEP AS NON CORE | Summary: Retained as a secondary, non-core phospholipase activity of LPL. Reason: LPL has experimentally supported glycerophospholipid phospholipase A1 activity, but it is low relative to its defining lipoprotein triacylglycerol lipase activity and its physiological contribution remains uncertain. |
| GO:0008970 glycerophospholipid phospholipase A1 activity | IDA PMID:7592706 Human hepatic and lipoprotein lipase: the loop covering the ... | KEEP AS NON CORE | Summary: Retained as a secondary, non-core phospholipase activity of LPL. Reason: LPL has experimentally supported glycerophospholipid phospholipase A1 activity, but it is low relative to its defining lipoprotein triacylglycerol lipase activity and its physiological contribution remains uncertain. |
| GO:0005515 protein binding | IPI PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is uninformative for LPL. Reason: The IPI assertion preserves an observed interaction, but GO:0005515 does not describe whether the partner supports secretion, endothelial transport, lipoprotein recognition, catalysis, or an incidental screen hit. It should not represent LPL function without a more informative interaction term. |
| GO:0045600 positive regulation of fat cell differentiation | IMP PMID:29794473 MiR-27b Impairs Adipocyte Differentiation of Human Adipose T... | KEEP AS NON CORE | Summary: Retained as non-core: Adipocyte differentiation is a developmental consequence of lipid delivery and signaling, not the core extracellular lipase reaction. Reason: Adipocyte differentiation is a developmental consequence of lipid delivery and signaling, not the core extracellular lipase reaction. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0043495 protein-membrane adaptor activity | TAS PMID:24608080 MicroRNA-27a/b regulates cellular cholesterol efflux, influx... | KEEP AS NON CORE | Summary: The extended macrophage lipid-storage use of LPL adaptor activity is retained as non-core. Reason: This assertion is specifically extended to a macrophage, has a lipoprotein-particle input, and is part of positive regulation of lipid storage; that cell-type-specific storage context is downstream and non-core. General protein-membrane adaptor activity at capillaries—where GPIHBP1-presented LPL captures triglyceride-rich particles at the endothelial cell surface—is a core noncatalytic function and is represented separately in the core-functions synthesis and GPIHBP1-supported replacement annotations. |
| GO:0031670 cellular response to nutrient | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as non-core: Nutrient response is a broad regulatory context downstream of LPL-dependent lipid delivery. Reason: Nutrient response is a broad regulatory context downstream of LPL-dependent lipid delivery. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cellular response to nutrient assignment for human LPL. |
| GO:0032731 positive regulation of interleukin-1 beta production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as non-core: Interleukin-1 beta production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Reason: Interleukin-1 beta production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of interleukin-1 beta production assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0032755 positive regulation of interleukin-6 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as non-core: Interleukin-6 production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Reason: Interleukin-6 production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of interleukin-6 production assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0032760 positive regulation of tumor necrosis factor production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as non-core: Tumor-necrosis-factor production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Reason: Tumor-necrosis-factor production is a context-dependent inflammatory consequence rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of tumor necrosis factor production assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0050729 positive regulation of inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as non-core: Inflammatory-response regulation is a context-dependent downstream role rather than direct LPL catalysis. Reason: Inflammatory-response regulation is a context-dependent downstream role rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of inflammatory response assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0071398 cellular response to fatty acid | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as non-core: Fatty-acid response is downstream of the fatty acids released by LPL and is not the defining molecular activity. Reason: Fatty-acid response is downstream of the fatty acids released by LPL and is not the defining molecular activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed cellular response to fatty acid assignment for human LPL. |
| GO:2000343 positive regulation of chemokine (C-X-C motif) ligand 2 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as non-core: CXCL2 regulation is a context-dependent inflammatory output rather than direct LPL catalysis. Reason: CXCL2 regulation is a context-dependent inflammatory output rather than direct LPL catalysis. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11152 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed positive regulation of chemokine (C-X-C motif) ligand 2 production assignment for human LPL. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0004465 lipoprotein lipase activity | IDA PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004465 lipoprotein lipase activity | IDA PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0005509 calcium ion binding | IDA PMID:16179346 Calcium triggers folding of lipoprotein lipase into active d... | ACCEPT | Summary: Accepted: Calcium-ion binding is experimentally supported and retained as a biochemical property without asserting that calcium is the primary catalytic cofactor. Reason: Calcium-ion binding is experimentally supported and retained as a biochemical property without asserting that calcium is the primary catalytic cofactor. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:16179346 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. |
| GO:0005509 calcium ion binding | IDA PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | ACCEPT | Summary: Accepted: Calcium-ion binding is experimentally supported and retained as a biochemical property without asserting that calcium is the primary catalytic cofactor. Reason: Calcium-ion binding is experimentally supported and retained as a biochemical property without asserting that calcium is the primary catalytic cofactor. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:16179346 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. |
| GO:0005576 extracellular region | IDA PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | IDA PMID:30559189 Structure of the lipoprotein lipase-GPIHBP1 complex that med... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0006631 fatty acid metabolic process | IDA PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | KEEP AS NON CORE | Summary: Retained as non-core: Fatty-acid metabolism is downstream of LPL-mediated fatty-acid release and is broader than the core reaction. Reason: Fatty-acid metabolism is downstream of LPL-mediated fatty-acid release and is broader than the core reaction. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0008201 heparin binding | IDA PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | ACCEPT | Summary: Accepted as a core-supported surface-binding activity of LPL. Reason: Heparin binding reports the basic surface that mediates physiologically important HSPG association, stability, tissue targeting, and transfer toward endothelial GPIHBP1. It supports the noncatalytic presentation and particle-bridging arm of LPL biology. Supporting Evidence: PMID:11342582 Thus, heparin association is required for LpL stability and normal physiologic functions. |
| GO:0019433 triglyceride catabolic process | IDA PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0034371 chylomicron remodeling | IMP PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | ACCEPT | Summary: Accepted: Chylomicron remodeling directly reflects hydrolysis of chylomicron triacylglycerol by extracellular LPL. Reason: Chylomicron remodeling directly reflects hydrolysis of chylomicron triacylglycerol by extracellular LPL. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0042803 protein homodimerization activity | IDA PMID:16179346 Calcium triggers folding of lipoprotein lipase into active d... | KEEP AS NON CORE | Summary: Retained as a non-core oligomeric property of LPL. Reason: Biochemical preparations support LPL homodimerization, but modern evidence also supports active GPIHBP1-stabilized monomeric LPL. Dimerization is therefore an accessory structural state rather than the defining molecular function. |
| GO:0043395 heparan sulfate proteoglycan binding | IMP PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | ACCEPT | Summary: Accepted: Heparan-sulfate-proteoglycan binding supports extracellular surface retention and particle bridging by LPL. Reason: Heparan-sulfate-proteoglycan binding supports extracellular surface retention and particle bridging by LPL. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:11342582 Thus, heparin association is required for LpL stability and normal physiologic functions. |
| GO:0071813 lipoprotein particle binding | IDA PMID:11342582 Heparin-binding defective lipoprotein lipase is unstable and... | ACCEPT | Summary: Accepted: Lipoprotein-particle binding directly describes LPL substrate-particle recognition. Reason: Lipoprotein-particle binding directly describes LPL substrate-particle recognition. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0004465 lipoprotein lipase activity | IDA PMID:27578112 Identification and characterization of two novel mutations i... | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0006631 fatty acid metabolic process | IDA PMID:27578112 Identification and characterization of two novel mutations i... | KEEP AS NON CORE | Summary: Retained as non-core: Fatty-acid metabolism is downstream of LPL-mediated fatty-acid release and is broader than the core reaction. Reason: Fatty-acid metabolism is downstream of LPL-mediated fatty-acid release and is broader than the core reaction. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0019433 triglyceride catabolic process | IDA PMID:27578112 Identification and characterization of two novel mutations i... | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0055096 low-density lipoprotein particle mediated signaling | IMP PMID:25149060 MicroRNA-590 attenuates lipid accumulation and pro-inflammat... | KEEP AS NON CORE | Summary: Retained as non-core: LDL-particle-mediated signaling is a context-dependent noncatalytic consequence of LPL-dependent particle interactions. Reason: LDL-particle-mediated signaling is a context-dependent noncatalytic consequence of LPL-dependent particle interactions. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0005576 extracellular region | IDA PMID:27578112 Identification and characterization of two novel mutations i... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0004465 lipoprotein lipase activity | IDA PMID:2110364 Lipoprotein lipaseBethesda: a single amino acid substitution... | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004465 lipoprotein lipase activity | IDA PMID:2340307 Rapid and simple isolation procedure for lipoprotein lipase ... | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0005576 extracellular region | IDA PMID:2340307 Rapid and simple isolation procedure for lipoprotein lipase ... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0008201 heparin binding | IDA PMID:2110364 Lipoprotein lipaseBethesda: a single amino acid substitution... | ACCEPT | Summary: Accepted as a core-supported surface-binding activity of LPL. Reason: Heparin binding reports the basic surface that mediates physiologically important HSPG association, stability, tissue targeting, and transfer toward endothelial GPIHBP1. It supports the noncatalytic presentation and particle-bridging arm of LPL biology. Supporting Evidence: PMID:11342582 Thus, heparin association is required for LpL stability and normal physiologic functions. |
| GO:0019433 triglyceride catabolic process | IDA PMID:2110364 Lipoprotein lipaseBethesda: a single amino acid substitution... | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0019433 triglyceride catabolic process | IDA PMID:2340307 Rapid and simple isolation procedure for lipoprotein lipase ... | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004465 lipoprotein lipase activity | IMP PMID:25149060 MicroRNA-590 attenuates lipid accumulation and pro-inflammat... | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0032722 positive regulation of chemokine production | IMP PMID:25149060 MicroRNA-590 attenuates lipid accumulation and pro-inflammat... | KEEP AS NON CORE | Summary: Retained as non-core: Chemokine production is a context-dependent inflammatory output rather than direct lipase activity. Reason: Chemokine production is a context-dependent inflammatory output rather than direct lipase activity. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. Human THP-1 macrophage experiments provide positive evidence that reducing LPL through miR-590 attenuates pro-inflammatory cytokine secretion. Supporting Evidence: PMID:25149060 We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. |
| GO:0042632 cholesterol homeostasis | IMP PMID:25149060 MicroRNA-590 attenuates lipid accumulation and pro-inflammat... | KEEP AS NON CORE | Summary: Retained as non-core: Cholesterol homeostasis is a systemic consequence of lipoprotein remodeling and clearance rather than the defining LPL reaction. Reason: Cholesterol homeostasis is a systemic consequence of lipoprotein remodeling and clearance rather than the defining LPL reaction. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0009749 response to glucose | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retained as non-core: Glucose response is a broad metabolic context inferred from an ortholog and is not core LPL activity. Reason: Glucose response is a broad metabolic context inferred from an ortholog and is not core LPL activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed response to glucose assignment for human LPL. |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0034185 apolipoprotein binding | IPI PMID:15178420 Mechanism of triglyceride lowering in mice expressing human ... | ACCEPT | Summary: Accepted: Apolipoprotein binding is informative for LPL activation and lipoprotein-particle recognition, including APOC2-dependent catalysis. Reason: Apolipoprotein binding is informative for LPL activation and lipoprotein-particle recognition, including APOC2-dependent catalysis. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:10727238 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. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-174757 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395768 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-560498 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784628 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784676 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6784861 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8857928 | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0070328 triglyceride homeostasis | IGI PMID:17018885 Reduction of plasma triglycerides in apolipoprotein C-II tra... | KEEP AS NON CORE | Summary: Retained as non-core: Triglyceride homeostasis is a physiological outcome of LPL catalysis and paralog/cofactor context, retained as non-core rather than as an activity definition. Reason: Triglyceride homeostasis is a physiological outcome of LPL catalysis and paralog/cofactor context, retained as non-core rather than as an activity definition. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0034371 chylomicron remodeling | IC PMID:3973011 Modulation of lipoprotein lipase activity by apolipoproteins... | ACCEPT | Summary: Accepted: Chylomicron remodeling directly reflects hydrolysis of chylomicron triacylglycerol by extracellular LPL. Reason: Chylomicron remodeling directly reflects hydrolysis of chylomicron triacylglycerol by extracellular LPL. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0004465 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed chylomicron remodeling assignment for human LPL. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0004465 lipoprotein lipase activity | IDA PMID:3973011 Modulation of lipoprotein lipase activity by apolipoproteins... | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | IDA PMID:182536 Effect of serum and C-apoproteins from very low density lipo... | UNDECIDED | Summary: The cached record does not permit verification that this experiment establishes the asserted LPL function. Reason: The project cache is title-only and the title concerns hepatic lipase; no accessible text establishes that LPL itself was assayed for this annotation. In accordance with curator-deference rules, the experimental assertion is not removed, but it remains undecided pending the full paper. |
| GO:0006633 fatty acid biosynthetic process | IDA PMID:182536 Effect of serum and C-apoproteins from very low density lipo... | MARK AS OVER ANNOTATED | Summary: Fatty-acid biosynthesis is downstream of, rather than catalyzed by, LPL. Reason: LPL hydrolyzes lipoprotein triacylglycerol and releases fatty acids. Those products can be re-esterified or used in biosynthesis, but LPL does not catalyze fatty-acid synthesis; this process assignment conflates substrate delivery with the biosynthetic pathway. |
| GO:0006633 fatty acid biosynthetic process | IC PMID:3973011 Modulation of lipoprotein lipase activity by apolipoproteins... | MARK AS OVER ANNOTATED | Summary: Fatty-acid biosynthesis is downstream of, rather than catalyzed by, LPL. Reason: LPL hydrolyzes lipoprotein triacylglycerol and releases fatty acids. Those products can be re-esterified or used in biosynthesis, but LPL does not catalyze fatty-acid synthesis; this process assignment conflates substrate delivery with the biosynthetic pathway. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: GO:0004465 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it does not establish the overextended fatty acid biosynthetic process assignment for human LPL. |
| GO:0019433 triglyceride catabolic process | IDA PMID:182536 Effect of serum and C-apoproteins from very low density lipo... | UNDECIDED | Summary: The cached record does not permit verification that this experiment establishes the asserted LPL function. Reason: The project cache is title-only and the title concerns hepatic lipase; no accessible text establishes that LPL itself was assayed for this annotation. In accordance with curator-deference rules, the experimental assertion is not removed, but it remains undecided pending the full paper. |
| GO:0019433 triglyceride catabolic process | IDA PMID:3973011 Modulation of lipoprotein lipase activity by apolipoproteins... | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0034372 very-low-density lipoprotein particle remodeling | IDA PMID:3973011 Modulation of lipoprotein lipase activity by apolipoproteins... | ACCEPT | Summary: Accepted: VLDL remodeling directly reflects hydrolysis of VLDL triacylglycerol by extracellular LPL. Reason: VLDL remodeling directly reflects hydrolysis of VLDL triacylglycerol by extracellular LPL. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:24726386 Both cell-culture and in vivo studies showed that TRL margination depends on LPL bound to GPIHBP1. |
| GO:0010886 positive regulation of cholesterol storage | IMP PMID:12573449 VLDL-induced triglyceride accumulation in human macrophages ... | KEEP AS NON CORE | Summary: Retained as non-core: Cholesterol storage is a macrophage-context consequence of lipoprotein uptake and is retained as non-core. Reason: Cholesterol storage is a macrophage-context consequence of lipoprotein uptake and is retained as non-core. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0006633 fatty acid biosynthetic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Fatty-acid biosynthesis is downstream of, rather than catalyzed by, LPL. Reason: LPL hydrolyzes lipoprotein triacylglycerol and releases fatty acids. Those products can be re-esterified or used in biosynthesis, but LPL does not catalyze fatty-acid synthesis; this process assignment conflates substrate delivery with the biosynthetic pathway. Propagation Review Root cause: PROPAGATION BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P11151 SUPPORTS SOURCE BUT NOT TARGET Exact WITH/FROM source; it does not establish the overextended fatty acid biosynthetic process assignment for human LPL. |
| GO:0019433 triglyceride catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Reason: Triglyceride catabolism is the immediate biological process driven by LPL hydrolysis of particle-associated triacylglycerol. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride catabolic process assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0004806 triacylglycerol lipase activity | IDA PMID:12573449 VLDL-induced triglyceride accumulation in human macrophages ... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:1371284 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. |
| GO:0005576 extracellular region | IDA PMID:12573449 VLDL-induced triglyceride accumulation in human macrophages ... | ACCEPT | Summary: Accepted: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. Reason: LPL is secreted and functions extracellularly on circulating lipoprotein particles at the vascular surface. The experimental assignment is biologically coherent and is retained with curator deference. Supporting Evidence: PMID:20620994 LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. |
| GO:0008201 heparin binding | IDA PMID:12573449 VLDL-induced triglyceride accumulation in human macrophages ... | ACCEPT | Summary: Accepted as a core-supported surface-binding activity of LPL. Reason: Heparin binding reports the basic surface that mediates physiologically important HSPG association, stability, tissue targeting, and transfer toward endothelial GPIHBP1. It supports the noncatalytic presentation and particle-bridging arm of LPL biology. Supporting Evidence: PMID:11342582 Thus, heparin association is required for LpL stability and normal physiologic functions. |
| GO:0005102 signaling receptor binding | IPI PMID:10085125 Sortilin/neurotensin receptor-3 binds and mediates degradati... | KEEP AS NON CORE | Summary: Retained as non-core: Signaling-receptor binding represents a noncatalytic particle-bridging interaction and is retained as non-core. Reason: Signaling-receptor binding represents a noncatalytic particle-bridging interaction and is retained as non-core. The experimental annotation is retained with curator deference; the available evidence does not justify overturning it. |
| GO:0004465 lipoprotein lipase activity | ISS PMID:10727238 Apolipoprotein C-II39-62 activates lipoprotein lipase by dir... | ACCEPT | Summary: Accepted: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Reason: Lipoprotein lipase activity is the defining LPL molecular function: hydrolysis of triacylglycerol carried in lipoprotein particles. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed lipoprotein lipase activity assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0004620 glycerophospholipase activity | ISS PMID:10727238 Apolipoprotein C-II39-62 activates lipoprotein lipase by dir... | KEEP AS NON CORE | Summary: Retained as a broad, secondary glycerophospholipase activity of LPL. Reason: LPL has low but detectable phospholipase activity, but its defining physiological reaction is hydrolysis of lipoprotein triacylglycerol. The broader glycerophospholipase assignment is therefore valid but non-core. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed glycerophospholipase activity assignment for human LPL. |
| GO:0004806 triacylglycerol lipase activity | ISS PMID:10727238 Apolipoprotein C-II39-62 activates lipoprotein lipase by dir... | ACCEPT | Summary: Accepted: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Reason: Triacylglycerol lipase activity accurately captures hydrolysis of triacylglycerol, although it is less particle-specific than lipoprotein lipase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triacylglycerol lipase activity assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0006641 triglyceride metabolic process | ISS PMID:10727238 Apolipoprotein C-II39-62 activates lipoprotein lipase by dir... | ACCEPT | Summary: Accepted: Triglyceride metabolism is a valid broader process encompassing LPL-mediated extracellular hydrolysis. Reason: Triglyceride metabolism is a valid broader process encompassing LPL-mediated extracellular hydrolysis. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed triglyceride metabolic process assignment for human LPL. Supporting Evidence: PMID:1371284 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. |
| GO:0006644 phospholipid metabolic process | ISS PMID:10727238 Apolipoprotein C-II39-62 activates lipoprotein lipase by dir... | KEEP AS NON CORE | Summary: Retained as non-core: Phospholipid metabolism is supported by secondary phospholipase activity but is not the dominant LPL process. Reason: Phospholipid metabolism is supported by secondary phospholipase activity but is not the dominant LPL process. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P11151 SUPPORTS TRANSFER Exact WITH/FROM source consistent with the reviewed phospholipid metabolic process assignment for human LPL. |
| GO:0008201 heparin binding | TAS PMID:1969408 Missense mutation (Gly→Glu188) of human lipoprotein lipase i... | ACCEPT | Summary: Accepted as a core-supported surface-binding activity of LPL. Reason: Heparin binding reports the basic surface that mediates physiologically important HSPG association, stability, tissue targeting, and transfer toward endothelial GPIHBP1. It supports the noncatalytic presentation and particle-bridging arm of LPL biology. Supporting Evidence: PMID:11342582 Thus, heparin association is required for LpL stability and normal physiologic functions. |
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Download this section (compressed HTML)Q: What fraction of active LPL is monomeric versus dimeric on the luminal surface of human capillaries, and how does GPIHBP1 or lipoprotein binding alter that balance?
Q: How much triglyceride-rich lipoprotein margination and tissue lipid uptake depends on LPL particle bridging independently of catalytic hydrolysis?
Q: Which molecular signals govern transfer of newly secreted LPL from interstitial HSPGs to endothelial GPIHBP1 in adipose tissue, skeletal muscle, and heart?
Q: How do APOC2 and the different ANGPTL complexes compete on native human GPIHBP1-LPL-lipoprotein assemblies across fasting and feeding states?
Q: Does the secondary phospholipase A1 activity of LPL materially influence chylomicron, VLDL, or HDL remodeling in vivo?
Q: Which reported LPL partners are stable physiological regulators or trafficking factors rather than high-throughput interaction-screen hits?
Experiment: Use endogenously tagged LPL and GPIHBP1 in perfused human microvascular organoids with single-particle imaging and cross-linking mass spectrometry to quantify LPL oligomeric state, endothelial transport, luminal residence, and lipoprotein margination.
Hypothesis: Native capillary LPL occupies dynamic GPIHBP1-stabilized monomeric and dimeric states whose proportions change upon triglyceride-rich particle engagement.
Experiment: Compare wild-type LPL with catalytically dead but secretion- and binding-competent LPL in human endothelial-parenchymal co-cultures, measuring particle margination, hydrolysis, remnant release, and fatty-acid uptake independently.
Hypothesis: GPIHBP1-bound LPL can support particle margination without catalysis, whereas efficient remnant formation and fatty-acid delivery require hydrolytic activity.
Experiment: Pulse-label LPL secreted by human myocytes or adipocytes and track its transfer through defined HSPG perturbations to endothelial GPIHBP1 under tissue-specific flow conditions.
Hypothesis: Interstitial HSPGs act as a mobile reservoir rather than a terminal anchor, with tissue-dependent sulfation patterns controlling transfer efficiency to GPIHBP1.
Experiment: Reconstitute human GPIHBP1-LPL-APOC2 lipoprotein particles and measure time-resolved inhibition, unfolding, and recovery after addition of ANGPTL3, ANGPTL4, or ANGPTL3-ANGPTL8 under matched lipid and temperature conditions.
Hypothesis: GPIHBP1 protection and ANGPTL inhibition depend on inhibitor identity, particle composition, and exposure kinetics rather than following a single absolute rule.
Experiment: Use reaction-selective lipidomics and catalytic-site mutants to separate LPL TAG lipase and phospholipase A1 flux in human plasma-particle remodeling assays.
Hypothesis: LPL phospholipase A1 activity contributes detectably to particle surface remodeling but accounts for substantially less physiological flux than TAG hydrolysis.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The distribution of active monomeric and dimeric LPL in native human capillaries, and whether oligomeric state changes with GPIHBP1, APOC2, particle binding, or ANGPTL exposure, remain unresolved.
Gap: The quantitative contributions of catalytic TAG hydrolysis versus noncatalytic GPIHBP1-dependent particle margination and receptor/proteoglycan bridging to tissue-specific lipid uptake have not been separated in humans.
Gap: How LPL moves from parenchymal-cell secretion sites through interstitial HSPGs to endothelial GPIHBP1 in different human tissues is incompletely defined, including the kinetics and regulation of each transfer step.
Gap: The relative effects of ANGPTL3, ANGPTL4, and ANGPTL3-ANGPTL8 complexes on GPIHBP1-bound human LPL across adipose, muscle, cardiac, and fasting/fed contexts remain uncertain; several decisive physiological studies are mouse-based.
Gap: The physiological contribution of LPL phospholipase A1 activity relative to its dominant triacylglycerol lipase activity is unknown, including which particle phospholipids are hydrolyzed in vivo.
Gap: Many reported LPL interaction partners come from high-throughput screens. Which interactions form reproducible, stoichiometric, and functionally consequential assemblies at endogenous abundance remains unresolved.
Gap: Variant studies distinguish defects in folding, secretion, GPIHBP1 or HSPG binding, particle recognition, and catalysis, but a systematic human genotype-to- biochemical-mechanism map is incomplete.
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