Apolipoprotein E is a secreted exchangeable apolipoprotein that associates with plasma, interstitial, and central-nervous-system lipoprotein particles. Through amphipathic lipid-binding domains and receptor-binding activity, APOE mediates cholesterol and phospholipid efflux, high-density lipoprotein particle formation/remodeling, and receptor- or proteoglycan-dependent clearance of chylomicron remnants, VLDL, IDL, LDL, and HDL particles. APOE is produced prominently by liver and by astrocytes and other glial cells in brain, where it supports lipid redistribution among cells. APOE also binds amyloid-beta, tau, immune receptors, extracellular matrix proteoglycans, and other partners, but these disease- or context-linked activities are secondary to its core lipid-transport and lipoprotein-clearance roles.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0120020 cholesterol transfer activity | IBA GO_REF:0000033 | ACCEPT | Summary: APOE cholesterol transfer activity is part of its core exchangeable apolipoprotein role in lipid and sterol transport. Reason: APOE lipid/phospholipid binding and cholesterol transfer underlie cholesterol/phospholipid efflux and HDL-like particle assembly. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0042627 chylomicron | IBA GO_REF:0000033 | ACCEPT | Summary: APOE is appropriately localized to chylomicron as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005543 phospholipid binding | IBA GO_REF:0000033 | ACCEPT | Summary: APOE phospholipid binding is part of its core exchangeable apolipoprotein role in lipid and sterol transport. Reason: APOE lipid/phospholipid binding and cholesterol transfer underlie cholesterol/phospholipid efflux and HDL-like particle assembly. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0008203 cholesterol metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: cholesterol metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0033344 cholesterol efflux | IBA GO_REF:0000033 | ACCEPT | Summary: cholesterol efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0033700 phospholipid efflux | IBA GO_REF:0000033 | ACCEPT | Summary: phospholipid efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0034361 very-low-density lipoprotein particle | IBA GO_REF:0000033 | ACCEPT | Summary: APOE is appropriately localized to very-low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034362 low-density lipoprotein particle | IBA GO_REF:0000033 | ACCEPT | Summary: APOE is appropriately localized to low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034364 high-density lipoprotein particle | IBA GO_REF:0000033 | ACCEPT | Summary: APOE is appropriately localized to high-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0055090 acylglycerol homeostasis | IBA GO_REF:0000033 | ACCEPT | Summary: acylglycerol homeostasis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0060228 phosphatidylcholine-sterol O-acyltransferase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: APOE can activate lecithin-cholesterol acyltransferase on apoB lipoproteins, a specific activity within its lipoprotein remodeling role. Reason: LCAT activation is a mechanistically specific APOE molecular function tied to cholesterol esterification and lipoprotein remodeling. Supporting Evidence: PMID:15654758 We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins. |
| GO:1903561 extracellular vesicle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: APOE localization to extracellular vesicle is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005771 multivesicular body | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: APOE localization to multivesicular body is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0006869 lipid transport | IEA GO_REF:0000002 | ACCEPT | Summary: lipid transport is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0008289 lipid binding | IEA GO_REF:0000002 | ACCEPT | Summary: APOE lipid binding is part of its core exchangeable apolipoprotein role in lipid and sterol transport. Reason: APOE lipid/phospholipid binding and cholesterol transfer underlie cholesterol/phospholipid efflux and HDL-like particle assembly. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0042157 lipoprotein metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: lipoprotein metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0098869 cellular oxidant detoxification | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: APOE-associated cellular oxidant detoxification is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. |
| GO:1903561 extracellular vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: APOE localization to extracellular vesicle is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0005515 protein binding | IPI PMID:12950167 Domains of apoE required for binding to apoE receptor 2 and ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:15182176 Two apolipoprotein E mimetic peptides, ApoE(130-149) and Apo... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:15615705 CLAC binds to amyloid beta peptides through the positively c... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:17116874 Blocking the apolipoprotein E/amyloid-beta interaction as a ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:19758344 Haptoglobin binds the antiatherogenic protein apolipoprotein... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:20030366 Decoding of lipoprotein-receptor interactions: properties of... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:21163940 Interactome mapping suggests new mechanistic details underly... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:21593558 The impact of a novel apolipoprotein E and amyloid-Ξ² protein... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:22528093 Search for amyloid-binding proteins by affinity chromatograp... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:24447298 LDL receptor/lipoprotein recognition: endosomal weakening of... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:25122793 Apolipoprotein E likely contributes to a maturation step of ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:26468283 Complement Factor H Binds to Human Serum Apolipoprotein E an... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:26921451 Effects of different isoforms of apoE on aggregation of the ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:28887769 Ξ±-Synuclein Interacts with Lipoproteins in Plasma. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:29507344 Effect of human very low-density lipoproteins on cardiotroph... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:30341064 High-affinity interactions and signal transduction between A... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:31270237 Ξ±-synuclein-lipoprotein interactions and elevated ApoE level... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:7566652 ApoE3 binding to tau tandem repeat I is abolished by tau ser... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of gene expression is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0010875 positive regulation of cholesterol efflux | IEA GO_REF:0000107 | ACCEPT | Summary: positive regulation of cholesterol efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0010877 lipid transport involved in lipid storage | IEA GO_REF:0000107 | ACCEPT | Summary: lipid transport involved in lipid storage is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0010976 positive regulation of neuron projection development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including positive regulation of neuron projection development, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0032438 melanosome organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: melanosome organization is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0034362 low-density lipoprotein particle | IEA GO_REF:0000120 | ACCEPT | Summary: APOE is appropriately localized to low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034372 very-low-density lipoprotein particle remodeling | IEA GO_REF:0000107 | ACCEPT | Summary: very-low-density lipoprotein particle remodeling is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0034374 low-density lipoprotein particle remodeling | IEA GO_REF:0000107 | ACCEPT | Summary: low-density lipoprotein particle remodeling is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: regulation of apoptotic process is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0043395 heparan sulfate proteoglycan binding | IEA GO_REF:0000107 | ACCEPT | Summary: APOE heparan sulfate proteoglycan binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0045088 regulation of innate immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: regulation of innate immune response is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0050728 negative regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: negative regulation of inflammatory response is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0050807 regulation of synapse organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including regulation of synapse organization, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0060228 phosphatidylcholine-sterol O-acyltransferase activator activity | IEA GO_REF:0000107 | ACCEPT | Summary: APOE can activate lecithin-cholesterol acyltransferase on apoB lipoproteins, a specific activity within its lipoprotein remodeling role. Reason: LCAT activation is a mechanistically specific APOE molecular function tied to cholesterol esterification and lipoprotein remodeling. Supporting Evidence: PMID:15654758 We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins. |
| GO:0070328 triglyceride homeostasis | IEA GO_REF:0000107 | ACCEPT | Summary: triglyceride homeostasis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0071813 lipoprotein particle binding | IEA GO_REF:0000107 | ACCEPT | Summary: APOE lipoprotein particle binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0071830 triglyceride-rich lipoprotein particle clearance | IEA GO_REF:0000107 | ACCEPT | Summary: triglyceride-rich lipoprotein particle clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0090205 positive regulation of cholesterol metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: positive regulation of cholesterol metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0097006 regulation of plasma lipoprotein particle levels | IEA GO_REF:0000107 | ACCEPT | Summary: regulation of plasma lipoprotein particle levels is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including glutamatergic synapse, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0120020 cholesterol transfer activity | IEA GO_REF:0000107 | ACCEPT | Summary: APOE cholesterol transfer activity is part of its core exchangeable apolipoprotein role in lipid and sterol transport. Reason: APOE lipid/phospholipid binding and cholesterol transfer underlie cholesterol/phospholipid efflux and HDL-like particle assembly. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:1900223 positive regulation of amyloid-beta clearance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for positive regulation of amyloid-beta clearance, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:1905907 negative regulation of amyloid fibril formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for negative regulation of amyloid fibril formation, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0001523 retinoid metabolic process | TAS Reactome:R-HSA-975634 | KEEP AS NON CORE | Summary: retinoid metabolic process is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0005576 extracellular region | EXP PMID:2498325 Glycosylation of human apolipoprotein E. The carbohydrate at... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | EXP PMID:30333625 LILRB4 signalling in leukaemia cells mediates T cell suppres... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:1903561 extracellular vesicle | EXP PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosome... | KEEP AS NON CORE | Summary: APOE localization to extracellular vesicle is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0050750 low-density lipoprotein particle receptor binding | TAS Reactome:R-HSA-2423785 | ACCEPT | Summary: APOE low-density lipoprotein particle receptor binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0005576 extracellular region | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0010642 negative regulation of platelet-derived growth factor receptor signaling pathway | IDA PMID:9685360 Apolipoprotein E inhibits platelet-derived growth factor-ind... | KEEP AS NON CORE | Summary: negative regulation of platelet-derived growth factor receptor signaling pathway is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:9685360 Taken together, these results suggest that apoE has cytostatic functions in the vessel wall |
| GO:0043409 negative regulation of MAPK cascade | IDA PMID:9685360 Apolipoprotein E inhibits platelet-derived growth factor-ind... | KEEP AS NON CORE | Summary: negative regulation of MAPK cascade is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:9685360 Taken together, these results suggest that apoE has cytostatic functions in the vessel wall |
| GO:0034360 chylomicron remnant | IDA PMID:7683668 Role of heparan sulfate proteoglycans in the binding and upt... | ACCEPT | Summary: APOE is appropriately localized to chylomicron remnant as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034361 very-low-density lipoprotein particle | IDA PMID:7683668 Role of heparan sulfate proteoglycans in the binding and upt... | ACCEPT | Summary: APOE is appropriately localized to very-low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0050728 negative regulation of inflammatory response | IDA PMID:8995232 Apolipoprotein E inhibits platelet aggregation through the L... | KEEP AS NON CORE | Summary: negative regulation of inflammatory response is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0140077 positive regulation of lipoprotein transport | IDA PMID:8300609 Secretion-capture role for apolipoprotein E in remnant lipop... | ACCEPT | Summary: positive regulation of lipoprotein transport is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0048018 receptor ligand activity | IDA PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... | KEEP AS NON CORE | Summary: receptor ligand activity is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:27477018 we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands of TREM2. |
| GO:0071402 cellular response to lipoprotein particle stimulus | IDA PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... | KEEP AS NON CORE | Summary: cellular response to lipoprotein particle stimulus is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0043083 synaptic cleft | IEP PMID:22637583 Apolipoprotein E4 effects in Alzheimer's disease are mediate... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including synaptic cleft, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0043083 synaptic cleft | IDA PMID:22637583 Apolipoprotein E4 effects in Alzheimer's disease are mediate... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including synaptic cleft, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0098978 glutamatergic synapse | IEP PMID:22637583 Apolipoprotein E4 effects in Alzheimer's disease are mediate... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including glutamatergic synapse, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0098978 glutamatergic synapse | IDA PMID:22637583 Apolipoprotein E4 effects in Alzheimer's disease are mediate... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including glutamatergic synapse, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0038060 nitric oxide-cGMP-mediated signaling | IDA PMID:8995232 Apolipoprotein E inhibits platelet aggregation through the L... | KEEP AS NON CORE | Summary: nitric oxide-cGMP-mediated signaling is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:8995232 We conclude that apoE inhibits platelet aggregation through the L-arginine:NO signal transduction pathway. |
| GO:0045429 positive regulation of nitric oxide biosynthetic process | IDA PMID:8995232 Apolipoprotein E inhibits platelet aggregation through the L... | KEEP AS NON CORE | Summary: positive regulation of nitric oxide biosynthetic process is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:8995232 We conclude that apoE inhibits platelet aggregation through the L-arginine:NO signal transduction pathway. |
| GO:0034382 chylomicron remnant clearance | IDA PMID:7683668 Role of heparan sulfate proteoglycans in the binding and upt... | ACCEPT | Summary: chylomicron remnant clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0034447 very-low-density lipoprotein particle clearance | IDA PMID:7683668 Role of heparan sulfate proteoglycans in the binding and upt... | ACCEPT | Summary: very-low-density lipoprotein particle clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0043395 heparan sulfate proteoglycan binding | IDA PMID:7683668 Role of heparan sulfate proteoglycans in the binding and upt... | ACCEPT | Summary: APOE heparan sulfate proteoglycan binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0045807 positive regulation of endocytosis | IDA PMID:7683668 Role of heparan sulfate proteoglycans in the binding and upt... | ACCEPT | Summary: positive regulation of endocytosis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Receptor-mediated uptake is an essential mechanism for clearance of APOE-containing lipoproteins and remnants. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0042803 protein homodimerization activity | IPI PMID:8089103 Isoform-specific binding of apolipoprotein E to beta-amyloid... | KEEP AS NON CORE | Summary: protein homodimerization activity reflects APOE oligomerization, structural participation, or disease-relevant binding rather than its primary lipid-transfer activity. Reason: Retain as non-core because APOE self-association and disease-relevant partner binding are real but less informative than specific lipid, receptor, and lipoprotein annotations. Supporting Evidence: PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0042803 protein homodimerization activity | IPI PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | KEEP AS NON CORE | Summary: protein homodimerization activity reflects APOE oligomerization, structural participation, or disease-relevant binding rather than its primary lipid-transfer activity. Reason: Retain as non-core because APOE self-association and disease-relevant partner binding are real but less informative than specific lipid, receptor, and lipoprotein annotations. Supporting Evidence: PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0097487 multivesicular body, internal vesicle | IDA PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosome... | KEEP AS NON CORE | Summary: APOE localization to multivesicular body, internal vesicle is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0005515 protein binding | IPI PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosome... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0032438 melanosome organization | IMP PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosome... | KEEP AS NON CORE | Summary: melanosome organization is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0042470 melanosome | IDA PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosome... | KEEP AS NON CORE | Summary: melanosome is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0070062 extracellular exosome | IDA PMID:26387950 Apolipoprotein E Regulates Amyloid Formation within Endosome... | KEEP AS NON CORE | Summary: APOE localization to extracellular exosome is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0019899 enzyme binding | IPI PMID:15654758 Apolipoprotein E is the major physiological activator of lec... | MARK AS OVER ANNOTATED | Summary: Generic enzyme binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0090205 positive regulation of cholesterol metabolic process | IDA PMID:15654758 Apolipoprotein E is the major physiological activator of lec... | ACCEPT | Summary: positive regulation of cholesterol metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0097113 AMPA glutamate receptor clustering | IDA PMID:24328732 ApoE4 delays dendritic spine formation during neuron develop... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including AMPA glutamate receptor clustering, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0097114 NMDA glutamate receptor clustering | IDA PMID:24328732 ApoE4 delays dendritic spine formation during neuron develop... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including NMDA glutamate receptor clustering, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IGI PMID:16805831 Inhibition of the canonical Wnt signaling pathway by apolipo... | KEEP AS NON CORE | Summary: negative regulation of canonical Wnt signaling pathway is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0048662 negative regulation of smooth muscle cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: negative regulation of smooth muscle cell proliferation is retained as non-core APOE-associated biology pending a deeper reference-specific adjudication. Reason: The annotation is not part of the primary lipid-transport and lipoprotein-clearance function set, but available local evidence was not sufficient to remove it. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976734 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0046983 protein dimerization activity | IPI PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | KEEP AS NON CORE | Summary: protein dimerization activity reflects APOE oligomerization, structural participation, or disease-relevant binding rather than its primary lipid-transfer activity. Reason: Retain as non-core because APOE self-association and disease-relevant partner binding are real but less informative than specific lipid, receptor, and lipoprotein annotations. Supporting Evidence: PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0060999 positive regulation of dendritic spine development | IDA PMID:24328732 ApoE4 delays dendritic spine formation during neuron develop... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including positive regulation of dendritic spine development, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:1902952 positive regulation of dendritic spine maintenance | IDA PMID:24328732 ApoE4 delays dendritic spine formation during neuron develop... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including positive regulation of dendritic spine maintenance, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0005102 signaling receptor binding | IPI PMID:27477018 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ,... | KEEP AS NON CORE | Summary: signaling receptor binding is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:27477018 we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands of TREM2. |
| GO:0043254 regulation of protein-containing complex assembly | IDA PMID:25207746 The binding of apolipoprotein E to oligomers and fibrils of ... | KEEP AS NON CORE | Summary: regulation of protein-containing complex assembly is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0044877 protein-containing complex binding | IDA PMID:25207746 The binding of apolipoprotein E to oligomers and fibrils of ... | MARK AS OVER ANNOTATED | Summary: Generic protein-containing complex binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0005515 protein binding | IPI PMID:30448281 Soluble LR11 competes with amyloid Ξ² in binding to cerebrosp... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:1902991 regulation of amyloid precursor protein catabolic process | IDA PMID:28164773 Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer'... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for regulation of amyloid precursor protein catabolic process, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:1900223 positive regulation of amyloid-beta clearance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for positive regulation of amyloid-beta clearance, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:1905907 negative regulation of amyloid fibril formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for negative regulation of amyloid fibril formation, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0010596 negative regulation of endothelial cell migration | IMP PMID:23142051 Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-de... | KEEP AS NON CORE | Summary: APOE-associated negative regulation of endothelial cell migration is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:9685360 Taken together, these results suggest that apoE has cytostatic functions in the vessel wall |
| GO:0050709 negative regulation of protein secretion | IMP PMID:27044754 FRMD4A-cytohesin signaling modulates the cellular release of... | KEEP AS NON CORE | Summary: negative regulation of protein secretion is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0031175 neuron projection development | IDA PMID:8939961 Apolipoprotein E-containing high density lipoprotein promote... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including neuron projection development, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0033344 cholesterol efflux | IDA PMID:23620513 ApoE influences amyloid-Ξ² (AΞ²) clearance despite minimal apo... | ACCEPT | Summary: cholesterol efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0042158 lipoprotein biosynthetic process | IDA PMID:23620513 ApoE influences amyloid-Ξ² (AΞ²) clearance despite minimal apo... | ACCEPT | Summary: lipoprotein biosynthetic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE contributes to HDL-like particle formation and lipoprotein remodeling through lipid binding, ABCA1-dependent efflux, and LCAT activation. Supporting Evidence: PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:14754908 ABCA1 is essential for the biogenesis of high density-sized lipoprotein containing only apoE particles in vivo. PMID:15654758 We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins. |
| GO:0043395 heparan sulfate proteoglycan binding | IDA PMID:23676495 Apolipoproteins E and AV mediate lipoprotein clearance by he... | ACCEPT | Summary: APOE heparan sulfate proteoglycan binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0071830 triglyceride-rich lipoprotein particle clearance | IMP PMID:23676495 Apolipoproteins E and AV mediate lipoprotein clearance by he... | ACCEPT | Summary: triglyceride-rich lipoprotein particle clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0034382 chylomicron remnant clearance | IDA PMID:1911868 Effects of exogenous apo E-3 and of cholesterol-enriched mea... | ACCEPT | Summary: chylomicron remnant clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0005576 extracellular region | IDA PMID:8340399 Discrete carboxyl-terminal segments of apolipoprotein E medi... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0031012 extracellular matrix | IDA PMID:9488694 The HepG2 extracellular matrix contains separate heparinase-... | ACCEPT | Summary: APOE is appropriately localized to extracellular matrix as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0042802 identical protein binding | IDA PMID:8340399 Discrete carboxyl-terminal segments of apolipoprotein E medi... | KEEP AS NON CORE | Summary: identical protein binding reflects APOE oligomerization, structural participation, or disease-relevant binding rather than its primary lipid-transfer activity. Reason: Retain as non-core because APOE self-association and disease-relevant partner binding are real but less informative than specific lipid, receptor, and lipoprotein annotations. Supporting Evidence: PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0043395 heparan sulfate proteoglycan binding | IDA PMID:9488694 The HepG2 extracellular matrix contains separate heparinase-... | ACCEPT | Summary: APOE heparan sulfate proteoglycan binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0071831 intermediate-density lipoprotein particle clearance | IDA PMID:1917954 Mechanisms of inhibition by apolipoprotein C of apolipoprote... | ACCEPT | Summary: intermediate-density lipoprotein particle clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0034447 very-low-density lipoprotein particle clearance | IDA PMID:2762297 Low density lipoprotein receptor-related protein mediates up... | ACCEPT | Summary: very-low-density lipoprotein particle clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0034361 very-low-density lipoprotein particle | IDA PMID:2280190 Apolipoprotein E distribution among human plasma lipoprotein... | ACCEPT | Summary: APOE is appropriately localized to very-low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034361 very-low-density lipoprotein particle | IDA PMID:8071364 Human apolipoprotein E. Role of arginine 61 in mediating the... | ACCEPT | Summary: APOE is appropriately localized to very-low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034362 low-density lipoprotein particle | IDA PMID:2280190 Apolipoprotein E distribution among human plasma lipoprotein... | ACCEPT | Summary: APOE is appropriately localized to low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034363 intermediate-density lipoprotein particle | IDA PMID:2280190 Apolipoprotein E distribution among human plasma lipoprotein... | ACCEPT | Summary: APOE is appropriately localized to intermediate-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034364 high-density lipoprotein particle | IDA PMID:2280190 Apolipoprotein E distribution among human plasma lipoprotein... | ACCEPT | Summary: APOE is appropriately localized to high-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034364 high-density lipoprotein particle | IDA PMID:8071364 Human apolipoprotein E. Role of arginine 61 in mediating the... | ACCEPT | Summary: APOE is appropriately localized to high-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005515 protein binding | IPI PMID:14754908 Molecular interactions between apoE and ABCA1: impact on apo... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0008201 heparin binding | IDA PMID:7635945 Dominant expression of type III hyperlipoproteinemia. Pathop... | ACCEPT | Summary: APOE heparin binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0034364 high-density lipoprotein particle | IDA PMID:14754908 Molecular interactions between apoE and ABCA1: impact on apo... | ACCEPT | Summary: APOE is appropriately localized to high-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034380 high-density lipoprotein particle assembly | IDA PMID:14754908 Molecular interactions between apoE and ABCA1: impact on apo... | ACCEPT | Summary: high-density lipoprotein particle assembly is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE contributes to HDL-like particle formation and lipoprotein remodeling through lipid binding, ABCA1-dependent efflux, and LCAT activation. Supporting Evidence: PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:14754908 ABCA1 is essential for the biogenesis of high density-sized lipoprotein containing only apoE particles in vivo. PMID:15654758 We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins. |
| GO:0050750 low-density lipoprotein particle receptor binding | IDA PMID:7635945 Dominant expression of type III hyperlipoproteinemia. Pathop... | ACCEPT | Summary: APOE low-density lipoprotein particle receptor binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0050750 low-density lipoprotein particle receptor binding | IDA PMID:1530612 Site-directed mutagenesis of an apolipoprotein E mutant, apo... | ACCEPT | Summary: APOE low-density lipoprotein particle receptor binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:28111074 ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcr... | KEEP AS NON CORE | Summary: positive regulation of DNA-templated transcription is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:28111074 ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases. |
| GO:0061136 regulation of proteasomal protein catabolic process | IMP PMID:28111074 ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcr... | KEEP AS NON CORE | Summary: regulation of proteasomal protein catabolic process is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:28111074 ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IMP PMID:28111074 ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcr... | KEEP AS NON CORE | Summary: positive regulation of ERK1 and ERK2 cascade is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. Supporting Evidence: PMID:28111074 ApoE binding to ApoE receptors activates dual leucine-zipper kinase (DLK), a MAP-kinase kinase kinase that then activates MKK7 and ERK1/2 MAP kinases. |
| GO:0005576 extracellular region | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0010629 negative regulation of gene expression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: negative regulation of gene expression is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0005576 extracellular region | ISS GO_REF:0000024 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0007616 long-term memory | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including long-term memory, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0035641 locomotory exploration behavior | IMP PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including locomotory exploration behavior, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0042632 cholesterol homeostasis | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | ACCEPT | Summary: cholesterol homeostasis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0051044 positive regulation of membrane protein ectodomain proteolysis | IGI PMID:25015123 Apolipoprotein E isoform-specific effects on lipoprotein rec... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for positive regulation of membrane protein ectodomain proteolysis, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0051246 regulation of protein metabolic process | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | KEEP AS NON CORE | Summary: regulation of protein metabolic process is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0061771 response to caloric restriction | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | KEEP AS NON CORE | Summary: response to caloric restriction is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0090181 regulation of cholesterol metabolic process | IGI PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | ACCEPT | Summary: regulation of cholesterol metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:2000822 regulation of behavioral fear response | IMP PMID:24412220 Apolipoprotein E-low density lipoprotein receptor interactio... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including regulation of behavioral fear response, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0034365 discoidal high-density lipoprotein particle | TAS PMID:22383525 Low-density lipoprotein receptor represents an apolipoprotei... | ACCEPT | Summary: APOE is appropriately localized to discoidal high-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0050750 low-density lipoprotein particle receptor binding | NAS PMID:20005821 Overexpression of low-density lipoprotein receptor in the br... | ACCEPT | Summary: APOE low-density lipoprotein particle receptor binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:1905908 positive regulation of amyloid fibril formation | TAS PMID:20005821 Overexpression of low-density lipoprotein receptor in the br... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for positive regulation of amyloid fibril formation, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0001540 amyloid-beta binding | IDA PMID:25207746 The binding of apolipoprotein E to oligomers and fibrils of ... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for amyloid-beta binding, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:1905906 regulation of amyloid fibril formation | IDA PMID:25207746 The binding of apolipoprotein E to oligomers and fibrils of ... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for regulation of amyloid fibril formation, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0001540 amyloid-beta binding | IPI PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for amyloid-beta binding, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0005198 structural molecule activity | TAS PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | KEEP AS NON CORE | Summary: structural molecule activity reflects APOE oligomerization, structural participation, or disease-relevant binding rather than its primary lipid-transfer activity. Reason: Retain as non-core because APOE self-association and disease-relevant partner binding are real but less informative than specific lipid, receptor, and lipoprotein annotations. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0006898 receptor-mediated endocytosis | TAS PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: receptor-mediated endocytosis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Receptor-mediated uptake is an essential mechanism for clearance of APOE-containing lipoproteins and remnants. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0034361 very-low-density lipoprotein particle | IDA PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: APOE is appropriately localized to very-low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034362 low-density lipoprotein particle | IDA PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: APOE is appropriately localized to low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034363 intermediate-density lipoprotein particle | IDA PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: APOE is appropriately localized to intermediate-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034364 high-density lipoprotein particle | IDA PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: APOE is appropriately localized to high-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:1905908 positive regulation of amyloid fibril formation | TAS PMID:9228033 Interaction of apolipoprotein J-amyloid beta-peptide complex... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for positive regulation of amyloid fibril formation, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:1990777 lipoprotein particle | IDA PMID:22138302 Preferential interactions between ApoE-containing lipoprotei... | ACCEPT | Summary: APOE is appropriately localized to lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0001540 amyloid-beta binding | IPI PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for amyloid-beta binding, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0042982 amyloid precursor protein metabolic process | IDA PMID:21593558 The impact of a novel apolipoprotein E and amyloid-Ξ² protein... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for amyloid precursor protein metabolic process, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0010976 positive regulation of neuron projection development | IDA PMID:7592957 Stable expression and secretion of apolipoproteins E3 and E4... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including positive regulation of neuron projection development, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0010977 negative regulation of neuron projection development | IDA PMID:7592957 Stable expression and secretion of apolipoproteins E3 and E4... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including negative regulation of neuron projection development, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:1905890 regulation of cellular response to very-low-density lipoprotein particle stimulus | IDA PMID:7592957 Stable expression and secretion of apolipoproteins E3 and E4... | ACCEPT | Summary: regulation of cellular response to very-low-density lipoprotein particle stimulus is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0010976 positive regulation of neuron projection development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including positive regulation of neuron projection development, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0010976 positive regulation of neuron projection development | IDA PMID:23845000 Isoform-specific effects of apoE on neurite outgrowth in olf... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including positive regulation of neuron projection development, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:1900272 negative regulation of long-term synaptic potentiation | IDA PMID:16273551 Blockade of nicotinic acetylcholine receptors suppresses hip... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including negative regulation of long-term synaptic potentiation, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0005576 extracellular region | IDA PMID:16805831 Inhibition of the canonical Wnt signaling pathway by apolipo... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0051248 negative regulation of protein metabolic process | IGI PMID:16805831 Inhibition of the canonical Wnt signaling pathway by apolipo... | KEEP AS NON CORE | Summary: negative regulation of protein metabolic process is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:16805831 Inhibition of the canonical Wnt signaling pathway by apolipo... | KEEP AS NON CORE | Summary: negative regulation of canonical Wnt signaling pathway is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | KEEP AS NON CORE | Summary: endoplasmic reticulum lumen is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0034361 very-low-density lipoprotein particle | IDA PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: APOE is appropriately localized to very-low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034362 low-density lipoprotein particle | IDA PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: APOE is appropriately localized to low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034363 intermediate-density lipoprotein particle | IDA PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: APOE is appropriately localized to intermediate-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034364 high-density lipoprotein particle | IDA PMID:9211985 Association of human, rat, and rabbit apolipoprotein E with ... | ACCEPT | Summary: APOE is appropriately localized to high-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0001540 amyloid-beta binding | IPI PMID:9003062 Characterization of the binding of amyloid-beta peptide to c... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for amyloid-beta binding, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0045807 positive regulation of endocytosis | IDA PMID:8300609 Secretion-capture role for apolipoprotein E in remnant lipop... | ACCEPT | Summary: positive regulation of endocytosis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Receptor-mediated uptake is an essential mechanism for clearance of APOE-containing lipoproteins and remnants. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0001540 amyloid-beta binding | IDA PMID:8089103 Isoform-specific binding of apolipoprotein E to beta-amyloid... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for amyloid-beta binding, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0005576 extracellular region | IDA PMID:8089103 Isoform-specific binding of apolipoprotein E to beta-amyloid... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0010877 lipid transport involved in lipid storage | ISS GO_REF:0000024 | ACCEPT | Summary: lipid transport involved in lipid storage is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0070328 triglyceride homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: triglyceride homeostasis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0005783 endoplasmic reticulum | IDA PMID:25122793 Apolipoprotein E likely contributes to a maturation step of ... | KEEP AS NON CORE | Summary: endoplasmic reticulum is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0005794 Golgi apparatus | IDA PMID:25122793 Apolipoprotein E likely contributes to a maturation step of ... | KEEP AS NON CORE | Summary: Golgi apparatus is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | TAS PMID:22988876 The importance of Wnt signalling for neurodegeneration in Pa... | KEEP AS NON CORE | Summary: negative regulation of canonical Wnt signaling pathway is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: APOE localization to extracellular vesicle is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0019068 virion assembly | IMP PMID:25122793 Apolipoprotein E likely contributes to a maturation step of ... | KEEP AS NON CORE | Summary: virion assembly is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0044794 host-mediated activation of viral process | IMP PMID:25122793 Apolipoprotein E likely contributes to a maturation step of ... | KEEP AS NON CORE | Summary: host-mediated activation of viral process is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: APOE localization to extracellular exosome is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: membrane is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:1903002 positive regulation of lipid transport across blood-brain barrier | IDA PMID:24345162 Reduction in DHA transport to the brain of mice expressing h... | ACCEPT | Summary: positive regulation of lipid transport across blood-brain barrier is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0046889 positive regulation of lipid biosynthetic process | IDA PMID:12042316 Apolipoprotein E (ApoE) isoform-dependent lipid release from... | ACCEPT | Summary: positive regulation of lipid biosynthetic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:1902995 positive regulation of phospholipid efflux | IDA PMID:12042316 Apolipoprotein E (ApoE) isoform-dependent lipid release from... | ACCEPT | Summary: positive regulation of phospholipid efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0010875 positive regulation of cholesterol efflux | IDA PMID:12042316 Apolipoprotein E (ApoE) isoform-dependent lipid release from... | ACCEPT | Summary: positive regulation of cholesterol efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0017038 protein import | IDA PMID:24446231 Apolipoproteins E and J interfere with amyloid-beta uptake b... | KEEP AS NON CORE | Summary: protein import is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:1900221 regulation of amyloid-beta clearance | IDA PMID:24446231 Apolipoproteins E and J interfere with amyloid-beta uptake b... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for regulation of amyloid-beta clearance, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0015909 long-chain fatty acid transport | IDA PMID:24345162 Reduction in DHA transport to the brain of mice expressing h... | ACCEPT | Summary: long-chain fatty acid transport is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0055089 fatty acid homeostasis | IDA PMID:24345162 Reduction in DHA transport to the brain of mice expressing h... | ACCEPT | Summary: fatty acid homeostasis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:1902430 negative regulation of amyloid-beta formation | IDA PMID:24154541 Human APOE genotype affects intraneuronal AΞ²1-42 accumulatio... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for negative regulation of amyloid-beta formation, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: nucleus is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0005515 protein binding | IPI PMID:8245722 Identification of disulfide-linked apolipoprotein species in... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0042803 protein homodimerization activity | IPI PMID:8245722 Identification of disulfide-linked apolipoprotein species in... | KEEP AS NON CORE | Summary: protein homodimerization activity reflects APOE oligomerization, structural participation, or disease-relevant binding rather than its primary lipid-transfer activity. Reason: Retain as non-core because APOE self-association and disease-relevant partner binding are real but less informative than specific lipid, receptor, and lipoprotein annotations. Supporting Evidence: PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0072562 blood microparticle | HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d... | ACCEPT | Summary: APOE is appropriately localized to blood microparticle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: APOE localization to extracellular exosome is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: APOE localization to extracellular exosome is supported, especially in extracellular vesicle and multivesicular-body contexts. Reason: This location is real and biologically useful, but it is secondary to APOE's core secreted lipoprotein-particle role. Supporting Evidence: PMID:26387950 Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-174657 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-174660 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-174690 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-174739 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-174757 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395768 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2395784 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2404131 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2423785 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2507854 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-266303 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8869590 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9031512 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9612243 | ACCEPT | Summary: APOE is appropriately localized to extracellular region as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0005769 early endosome | TAS Reactome:R-HSA-2404131 | KEEP AS NON CORE | Summary: early endosome is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0005769 early endosome | TAS Reactome:R-HSA-2404140 | KEEP AS NON CORE | Summary: early endosome is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0005769 early endosome | TAS Reactome:R-HSA-2429643 | KEEP AS NON CORE | Summary: early endosome is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-174657 | KEEP AS NON CORE | Summary: plasma membrane is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-174706 | KEEP AS NON CORE | Summary: plasma membrane is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-174706 | KEEP AS NON CORE | Summary: clathrin-coated endocytic vesicle membrane is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0071682 endocytic vesicle lumen | TAS Reactome:R-HSA-2507854 | KEEP AS NON CORE | Summary: endocytic vesicle lumen is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0032489 regulation of Cdc42 protein signal transduction | IDA PMID:16443932 Apolipoprotein A-I activates Cdc42 signaling through the ABC... | KEEP AS NON CORE | Summary: regulation of Cdc42 protein signal transduction is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0034361 very-low-density lipoprotein particle | IDA PMID:17154273 Proteomic analysis of human very low-density lipoprotein by ... | ACCEPT | Summary: APOE is appropriately localized to very-low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034372 very-low-density lipoprotein particle remodeling | IDA PMID:15654758 Apolipoprotein E is the major physiological activator of lec... | ACCEPT | Summary: very-low-density lipoprotein particle remodeling is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0060228 phosphatidylcholine-sterol O-acyltransferase activator activity | IDA PMID:15654758 Apolipoprotein E is the major physiological activator of lec... | ACCEPT | Summary: APOE can activate lecithin-cholesterol acyltransferase on apoB lipoproteins, a specific activity within its lipoprotein remodeling role. Reason: LCAT activation is a mechanistically specific APOE molecular function tied to cholesterol esterification and lipoprotein remodeling. Supporting Evidence: PMID:15654758 We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins. |
| GO:0045541 negative regulation of cholesterol biosynthetic process | IDA PMID:1917954 Mechanisms of inhibition by apolipoprotein C of apolipoprote... | ACCEPT | Summary: negative regulation of cholesterol biosynthetic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0005319 lipid carrier activity | IDA PMID:17305370 The C-terminal lipid-binding domain of apolipoprotein E is a... | ACCEPT | Summary: APOE lipid carrier activity is part of its core exchangeable apolipoprotein role in lipid and sterol transport. Reason: APOE lipid/phospholipid binding and cholesterol transfer underlie cholesterol/phospholipid efflux and HDL-like particle assembly. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0034380 high-density lipoprotein particle assembly | IDA PMID:17305370 The C-terminal lipid-binding domain of apolipoprotein E is a... | ACCEPT | Summary: high-density lipoprotein particle assembly is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE contributes to HDL-like particle formation and lipoprotein remodeling through lipid binding, ABCA1-dependent efflux, and LCAT activation. Supporting Evidence: PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:14754908 ABCA1 is essential for the biogenesis of high density-sized lipoprotein containing only apoE particles in vivo. PMID:15654758 We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins. |
| GO:0034384 high-density lipoprotein particle clearance | IDA PMID:210175 Apoprotein (E--A-II) complex of human plasma lipoproteins. I... | ACCEPT | Summary: high-density lipoprotein particle clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE contributes to HDL-like particle formation and lipoprotein remodeling through lipid binding, ABCA1-dependent efflux, and LCAT activation. Supporting Evidence: PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:14754908 ABCA1 is essential for the biogenesis of high density-sized lipoprotein containing only apoE particles in vivo. PMID:15654758 We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins. |
| GO:0010875 positive regulation of cholesterol efflux | IGI PMID:12401887 Evidence for differential effects of apoE3 and apoE4 on HDL ... | ACCEPT | Summary: positive regulation of cholesterol efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0010875 positive regulation of cholesterol efflux | IDA PMID:14754908 Molecular interactions between apoE and ABCA1: impact on apo... | ACCEPT | Summary: positive regulation of cholesterol efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0034372 very-low-density lipoprotein particle remodeling | IGI PMID:12401887 Evidence for differential effects of apoE3 and apoE4 on HDL ... | ACCEPT | Summary: very-low-density lipoprotein particle remodeling is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0034375 high-density lipoprotein particle remodeling | IGI PMID:12401887 Evidence for differential effects of apoE3 and apoE4 on HDL ... | ACCEPT | Summary: high-density lipoprotein particle remodeling is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE contributes to HDL-like particle formation and lipoprotein remodeling through lipid binding, ABCA1-dependent efflux, and LCAT activation. Supporting Evidence: PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:14754908 ABCA1 is essential for the biogenesis of high density-sized lipoprotein containing only apoE particles in vivo. PMID:15654758 We conclude that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins. |
| GO:0070326 very-low-density lipoprotein particle receptor binding | IPI PMID:12950167 Domains of apoE required for binding to apoE receptor 2 and ... | ACCEPT | Summary: APOE very-low-density lipoprotein particle receptor binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0070326 very-low-density lipoprotein particle receptor binding | IDA PMID:1384047 Rabbit very low density lipoprotein receptor: a low density ... | ACCEPT | Summary: APOE very-low-density lipoprotein particle receptor binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0006898 receptor-mediated endocytosis | IDA PMID:1917954 Mechanisms of inhibition by apolipoprotein C of apolipoprote... | ACCEPT | Summary: receptor-mediated endocytosis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Receptor-mediated uptake is an essential mechanism for clearance of APOE-containing lipoproteins and remnants. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0034447 very-low-density lipoprotein particle clearance | IDA PMID:1917954 Mechanisms of inhibition by apolipoprotein C of apolipoprote... | ACCEPT | Summary: very-low-density lipoprotein particle clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0034447 very-low-density lipoprotein particle clearance | IMP PMID:9649566 Type III hyperlipoproteinemia and spontaneous atherosclerosi... | ACCEPT | Summary: very-low-density lipoprotein particle clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0032805 positive regulation of low-density lipoprotein particle receptor catabolic process | IDA PMID:15950758 Regulation of ApoE receptor proteolysis by ligand binding. | ACCEPT | Summary: positive regulation of low-density lipoprotein particle receptor catabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Receptor-mediated uptake is an essential mechanism for clearance of APOE-containing lipoproteins and remnants. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0042802 identical protein binding | IDA PMID:4066713 Behavior of human apolipoprotein E in aqueous solutions and ... | KEEP AS NON CORE | Summary: identical protein binding reflects APOE oligomerization, structural participation, or disease-relevant binding rather than its primary lipid-transfer activity. Reason: Retain as non-core because APOE self-association and disease-relevant partner binding are real but less informative than specific lipid, receptor, and lipoprotein annotations. Supporting Evidence: PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0034361 very-low-density lipoprotein particle | IDA PMID:8245722 Identification of disulfide-linked apolipoprotein species in... | ACCEPT | Summary: APOE is appropriately localized to very-low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034362 low-density lipoprotein particle | IDA PMID:8245722 Identification of disulfide-linked apolipoprotein species in... | ACCEPT | Summary: APOE is appropriately localized to low-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034363 intermediate-density lipoprotein particle | IDA PMID:17336988 Fractionation of cholesteryl ester rich intermediate density... | ACCEPT | Summary: APOE is appropriately localized to intermediate-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034364 high-density lipoprotein particle | IDA PMID:210174 Apoprotein (E--A-II) complex of human plasma lipoproteins. I... | ACCEPT | Summary: APOE is appropriately localized to high-density lipoprotein particle as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0034382 chylomicron remnant clearance | IMP PMID:7175379 Studies of familial type III hyperlipoproteinemia using as a... | ACCEPT | Summary: chylomicron remnant clearance is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: APOE-dependent receptor and proteoglycan interactions support remnant and triglyceride-rich lipoprotein clearance. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0033344 cholesterol efflux | IDA PMID:11162594 Apolipoprotein specificity for lipid efflux by the human ABC... | ACCEPT | Summary: cholesterol efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0033700 phospholipid efflux | IDA PMID:11162594 Apolipoprotein specificity for lipid efflux by the human ABC... | ACCEPT | Summary: phospholipid efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0010544 negative regulation of platelet activation | IDA PMID:8995232 Apolipoprotein E inhibits platelet aggregation through the L... | KEEP AS NON CORE | Summary: APOE-associated negative regulation of platelet activation is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8995232 We conclude that apoE inhibits platelet aggregation through the L-arginine:NO signal transduction pathway. |
| GO:0005737 cytoplasm | NAS PMID:8083695 Apolipoprotein E is localized to the cytoplasm of human cort... | KEEP AS NON CORE | Summary: cytoplasm is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0030425 dendrite | NAS PMID:8083695 Apolipoprotein E is localized to the cytoplasm of human cort... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including dendrite, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0043025 neuronal cell body | NAS PMID:8083695 Apolipoprotein E is localized to the cytoplasm of human cort... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including neuronal cell body, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0048156 tau protein binding | IPI PMID:7566652 ApoE3 binding to tau tandem repeat I is abolished by tau ser... | KEEP AS NON CORE | Summary: tau protein binding reflects APOE oligomerization, structural participation, or disease-relevant binding rather than its primary lipid-transfer activity. Reason: Retain as non-core because APOE self-association and disease-relevant partner binding are real but less informative than specific lipid, receptor, and lipoprotein annotations. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0001937 negative regulation of endothelial cell proliferation | IDA PMID:9685360 Apolipoprotein E inhibits platelet-derived growth factor-ind... | KEEP AS NON CORE | Summary: APOE-associated negative regulation of endothelial cell proliferation is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:9685360 Taken together, these results suggest that apoE has cytostatic functions in the vessel wall |
| GO:0016209 antioxidant activity | IDA PMID:9685360 Apolipoprotein E inhibits platelet-derived growth factor-ind... | KEEP AS NON CORE | Summary: APOE-associated antioxidant activity is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. |
| GO:0030195 negative regulation of blood coagulation | IDA PMID:8995232 Apolipoprotein E inhibits platelet aggregation through the L... | KEEP AS NON CORE | Summary: APOE-associated negative regulation of blood coagulation is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8995232 We conclude that apoE inhibits platelet aggregation through the L-arginine:NO signal transduction pathway. |
| GO:0043537 negative regulation of blood vessel endothelial cell migration | IDA PMID:9685360 Apolipoprotein E inhibits platelet-derived growth factor-ind... | KEEP AS NON CORE | Summary: APOE-associated negative regulation of blood vessel endothelial cell migration is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:9685360 Taken together, these results suggest that apoE has cytostatic functions in the vessel wall |
| GO:0043691 reverse cholesterol transport | IDA PMID:8127890 A plasma lipoprotein containing only apolipoprotein E and wi... | ACCEPT | Summary: reverse cholesterol transport is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0046911 metal chelating activity | IDA PMID:9685360 Apolipoprotein E inhibits platelet-derived growth factor-ind... | KEEP AS NON CORE | Summary: APOE-associated metal chelating activity is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. |
| GO:0005543 phospholipid binding | IDA PMID:4066713 Behavior of human apolipoprotein E in aqueous solutions and ... | ACCEPT | Summary: APOE phospholipid binding is part of its core exchangeable apolipoprotein role in lipid and sterol transport. Reason: APOE lipid/phospholipid binding and cholesterol transfer underlie cholesterol/phospholipid efflux and HDL-like particle assembly. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0006641 triglyceride metabolic process | IMP PMID:3771793 Familial apolipoprotein E deficiency. | ACCEPT | Summary: triglyceride metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0006641 triglyceride metabolic process | IDA PMID:9649566 Type III hyperlipoproteinemia and spontaneous atherosclerosi... | ACCEPT | Summary: triglyceride metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0008201 heparin binding | IDA PMID:2745454 Apolipoprotein E mediates binding of normal very low density... | ACCEPT | Summary: APOE heparin binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0008203 cholesterol metabolic process | IMP PMID:3771793 Familial apolipoprotein E deficiency. | ACCEPT | Summary: cholesterol metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0008203 cholesterol metabolic process | IDA PMID:9649566 Type III hyperlipoproteinemia and spontaneous atherosclerosi... | ACCEPT | Summary: cholesterol metabolic process is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0042627 chylomicron | IDA PMID:16935699 Apolipoprotein E enrichment of immuno-separated chylomicron ... | ACCEPT | Summary: APOE is appropriately localized to chylomicron as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0042632 cholesterol homeostasis | IDA PMID:9649566 Type III hyperlipoproteinemia and spontaneous atherosclerosi... | ACCEPT | Summary: cholesterol homeostasis is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: This process falls within APOE's core role in lipid transport, lipoprotein particle metabolism, and lipid homeostasis. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE |
| GO:0050750 low-density lipoprotein particle receptor binding | IDA PMID:210175 Apoprotein (E--A-II) complex of human plasma lipoproteins. I... | ACCEPT | Summary: APOE low-density lipoprotein particle receptor binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0051044 positive regulation of membrane protein ectodomain proteolysis | IDA PMID:15950758 Regulation of ApoE receptor proteolysis by ligand binding. | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for positive regulation of membrane protein ectodomain proteolysis, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0050750 low-density lipoprotein particle receptor binding | IPI PMID:17326667 Apolipoprotein A-V interaction with members of the low densi... | ACCEPT | Summary: APOE low-density lipoprotein particle receptor binding supports receptor- or proteoglycan-dependent uptake of APOE-containing lipoprotein particles. Reason: Receptor and HSPG interactions are central to APOE-mediated lipoprotein clearance and particle uptake. Supporting Evidence: PMID:2762297 We conclude that LRP can mediate the cellular uptake and lysosomal hydrolysis of cholesteryl esters contained in lipoproteins that are enriched in apo E. PMID:7635945 ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. PMID:23676495 We conclude that clearance of TRLs by hepatic HSPGs is atheroprotective and mediated by multivalent binding to ApoE and ApoAV. |
| GO:0042627 chylomicron | IDA PMID:8245722 Identification of disulfide-linked apolipoprotein species in... | ACCEPT | Summary: APOE is appropriately localized to chylomicron as a secreted apolipoprotein associated with plasma and tissue lipoprotein particles. Reason: Extracellular and lipoprotein-particle component annotations capture APOE's core site of action in lipid transport and lipoprotein clearance. Supporting Evidence: PMID:8340399 These results indicate lipoprotein association modulates the clearance of apoE PMID:9488694 Exogenously applied lipid-free apoE readily bound to the ECM; however, increasing the lipid content decreased its association. |
| GO:0007186 G protein-coupled receptor signaling pathway | IDA PMID:16443932 Apolipoprotein A-I activates Cdc42 signaling through the ABC... | KEEP AS NON CORE | Summary: G protein-coupled receptor signaling pathway is plausible APOE-associated signaling or regulatory biology, but it is not the core apolipoprotein function. Reason: Retain as non-core because APOE can signal through receptors and alter downstream pathways, but these are context-dependent consequences of APOE-lipoprotein or receptor interactions. |
| GO:0033344 cholesterol efflux | IDA PMID:16443932 Apolipoprotein A-I activates Cdc42 signaling through the ABC... | ACCEPT | Summary: cholesterol efflux is part of APOE's core lipoprotein transport, remodeling, or clearance biology. Reason: Cholesterol and phospholipid efflux are well-supported APOE functions in peripheral and CNS-relevant cell systems. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. |
| GO:0005515 protein binding | IPI PMID:7972031 Isoform-specific interactions of apolipoprotein E with micro... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for APOE. Reason: The underlying interaction may be real, but this term is too generic for APOE; specific receptor binding, lipoprotein particle binding, amyloid-beta binding, tau binding, or lipid-transfer terms are more informative. |
| GO:0008289 lipid binding | IDA PMID:4066713 Behavior of human apolipoprotein E in aqueous solutions and ... | ACCEPT | Summary: APOE lipid binding is part of its core exchangeable apolipoprotein role in lipid and sterol transport. Reason: APOE lipid/phospholipid binding and cholesterol transfer underlie cholesterol/phospholipid efflux and HDL-like particle assembly. Supporting Evidence: PMID:11162594 ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. PMID:17305370 the CT lipid-binding domain of apoE encompassing amino acids 222-299 is necessary and sufficient for mediating ABCA1 lipid efflux and HDL particle assembly. PMID:4066713 The results are consistent with a model that amphiphilic alpha-helical conformation is responsible both for self-association and surface binding |
| GO:0001540 amyloid-beta binding | IDA PMID:11305869 Quantitation of apoE domains in Alzheimer disease brain sugg... | KEEP AS NON CORE | Summary: APOE has credible Alzheimer-relevant evidence for amyloid-beta binding, but this is secondary to its core apolipoprotein lipid-transport role. Reason: Amyloid-related annotations should be retained as disease-relevant non-core biology rather than treated as APOE's primary evolved molecular function. Supporting Evidence: PMID:25207746 apoE binds primarily to and affects the growth of oligomers that lead to the nuclei required for fibril growth. |
| GO:0005737 cytoplasm | TAS PMID:9622609 The neurobiology of apolipoproteins and their receptors in t... | KEEP AS NON CORE | Summary: cytoplasm is retained as APOE-associated contextual biology, not as the core apolipoprotein activity. Reason: This annotation is not central to APOE lipid transport or lipoprotein clearance but is plausible enough to retain outside the core function set. |
| GO:0007271 synaptic transmission, cholinergic | TAS PMID:9622609 The neurobiology of apolipoproteins and their receptors in t... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including synaptic transmission, cholinergic, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0030516 regulation of axon extension | TAS PMID:9622609 The neurobiology of apolipoproteins and their receptors in t... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including regulation of axon extension, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
| GO:0000302 response to reactive oxygen species | NAS PMID:11743999 Apolipoprotein E modulates Alzheimer's Abeta(1-42)-induced o... | KEEP AS NON CORE | Summary: APOE-associated response to reactive oxygen species is secondary vascular, antioxidant, or stress-response biology. Reason: This annotation has plausible experimental support but should not be promoted above APOE's primary role in lipid transport and lipoprotein clearance. |
| GO:0007010 cytoskeleton organization | TAS PMID:9622609 The neurobiology of apolipoproteins and their receptors in t... | KEEP AS NON CORE | Summary: cytoskeleton organization is retained as non-core APOE-associated biology pending a deeper reference-specific adjudication. Reason: The annotation is not part of the primary lipid-transport and lipoprotein-clearance function set, but available local evidence was not sufficient to remove it. |
| GO:0048168 regulation of neuronal synaptic plasticity | TAS PMID:9622609 The neurobiology of apolipoproteins and their receptors in t... | KEEP AS NON CORE | Summary: APOE influences neuronal or synaptic phenotypes including regulation of neuronal synaptic plasticity, largely through CNS lipid transport and receptor-dependent contexts. Reason: Retain as non-core pleiotropic CNS biology; these annotations describe downstream or cell-context phenotypes rather than APOE's primary apolipoprotein molecular activity. Supporting Evidence: PMID:12042316 Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. PMID:24345162 Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. |
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Download this section (compressed HTML)Q: Which APOE receptor-binding and proteoglycan-binding annotations should be separated by particle class, tissue, and receptor family in normal in-vivo lipid clearance?
Suggested experts: lipoprotein metabolism curators, cardiovascular lipid biology experts
Q: Which CNS APOE phenotypes are direct consequences of astrocyte/glial lipid transport versus downstream effects of amyloid, tau, inflammatory, or synaptic disease-model systems?
Suggested experts: neurobiology curators, Alzheimer lipid biology experts
Q: How should APOE amyloid-beta, tau, TREM2/LILRB4, and extracellular-vesicle annotations be represented without obscuring the core apolipoprotein lipid-transfer function?
Suggested experts: GO amyloid biology curators, microglial lipid signaling experts
Experiment: Use endogenous APOE isoform knock-in hepatocyte, macrophage, astrocyte, and microglial systems with particle-resolved lipidomics to distinguish APOE-dependent lipid efflux, particle assembly, and particle clearance outputs.
Hypothesis: APOE core functions differ by cell type and lipoprotein particle class, but converge on lipid loading, receptor/proteoglycan binding, and clearance.
Type: endogenous isoform knock-in lipidomics and particle proteomics
Experiment: Quantify APOE-containing extracellular vesicle and multivesicular-body pools separately from classical lipoprotein particles under baseline physiological conditions.
Hypothesis: APOE vesicle localization is a real but context-specific pool that should be curated separately from bulk secreted lipoprotein-particle APOE.
Type: subcellular fractionation and vesicle proteomics
Experiment: Compare amyloid-beta, tau, and TREM2/LILRB4 binding assays using lipid-free APOE, defined lipidated particles, and endogenous CNS APOE particles.
Hypothesis: Many disease-relevant APOE interactions depend on lipidation state and particle context, and should not be collapsed into generic protein binding.
Type: particle-defined binding and uptake assays
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