BioPAX pathway converted from "Chylomicron clearance" in the Reactome database. Chylomicron clearance Chylomicron clearance Circulating chylomicrons acquire molecules of apolipoproteins C and E and through interaction with endothelial lipases lose a large fraction of their triacylglycerol. These changes convert them to chylomicron remnants which bind to LDL receptors, primarily on the surfaces of liver cells, clearing them from the circulation.<br>This binding and clearance process involves several steps and requires the presence of heparan sulfate proteoglycan (HSPG)-associated hepatic lipase (HL). The molecular details of LDLR binding, and of the following steps of remnant endocytosis, are inferred from those of the coorresponding step of LDLR-mediated low-density lipoprotein (LDL) endocytosis (Redgrave 2004). Authored: D'Eustachio, P, 2007-04-30 14:19:38 Reviewed: Jassal, Bijay, 2016-01-27 Edited: D'Eustachio, P, 2007-04-30 14:19:38 chylomicron remnant:apoE complex + LDLR => chylomicron remnant:apoE:LDLR complex chylomicron remnant:apoE complex + LDLR => chylomicron remnant:apoE:LDLR complex Chylomicron micron remnants containing apolipoprotein E associate with the surfaces of cells in a process that probably involves several steps and that requires the presence (but not the catalytic activity) of heparan sulfate proteoglycan (HSPG)-associated hepatic lipase (HL). This process ultimately results in binding of the remnant to cell-surface LDL receptors (LDLR) (Ji et al. 1994). The molecular details of LDLR binding, and of the following steps of remnant endocytosis, are inferred from those of the coorresponding step of LDLR-mediated low-density lipoprotein (LDL) endocytosis. In the body, this process occurs in the liver. Authored: D'Eustachio, P, 2007-04-30 14:19:38 Edited: D'Eustachio, P, 2006-02-20 18:35:05 Reactome DB_ID: 171053 1 plasma membrane GO 0005886 UniProt:P01130 LDLR LDLR LDLR FUNCTION Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits.FUNCTION (Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins.FUNCTION (Microbial infection) Acts as a receptor for Vesicular stomatitis virus.FUNCTION (Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.SUBUNIT Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (By similarity). Interacts (via NPXY motif) with LDLRAP1 (via PID domain) (PubMed:12221107, PubMed:22509010). Interacts with ARRB1 (PubMed:12944399). Interacts with SNX17 (PubMed:14739284). Interacts with the full-length immature form of PCSK9 (via C-terminus) (PubMed:17461796, PubMed:21149300).SUBUNIT (Microbial infection) Interacts with C.difficile toxin TcdA, suggesting that it may contribute to TcdA toxin entry into cells.SUBUNIT (Microbial infection) Interacts with vesicular stomatitis virus glycoprotein.SUBUNIT (Microbial infection) May interact with HIV-1 Tat.DOMAIN The NPXY motif mediates the interaction with the clathrin adapter DAB2 and with LDLRAP1 which are involved in receptor internalization. A few residues outside the motif also play a role in the interaction.PTM N- and O-glycosylated.PTM Ubiquitinated by MYLIP leading to degradation.SIMILARITY Belongs to the LDLR family. Reactome http://www.reactome.org Homo sapiens NCBI Taxonomy 9606 UniProt P01130 Chain Coordinates 22 EQUAL 860 EQUAL Reactome DB_ID: 174792 1 extracellular region GO 0005576 chylomicron remnant:apoE complex [extracellular region] chylomicron remnant:apoE complex Reactome DB_ID: 174646 1 UniProt:P02649 APOE APOE APOE FUNCTION APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:6860692, PubMed:1911868, PubMed:14754908). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:6860692, PubMed:2762297, PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:14754908, PubMed:23620513). Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:6860692, PubMed:2762297, PubMed:9395455). As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) (PubMed:6860692, PubMed:1911868). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (PubMed:2762297, PubMed:1917954, PubMed:7768901, PubMed:8939961, PubMed:12950167, PubMed:20030366, PubMed:2063194, PubMed:8756331, PubMed:20303980, PubMed:1530612, PubMed:7635945). Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:9395455, PubMed:9488694, PubMed:23676495, PubMed:7635945). A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:23676495, PubMed:29516132). APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues (PubMed:2762297, PubMed:29516132). By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis (PubMed:2762297, PubMed:1917954, PubMed:29516132). APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis (PubMed:9395455, PubMed:14754908, PubMed:23620513). First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513). Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes (PubMed:9395455). APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting (PubMed:8939961, PubMed:25173806). APOE is also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). Binds to the immune cell receptor LILRB4 (PubMed:30333625). APOE may also play a role in transcription regulation through a receptor-dependent and cholesterol-independent mechanism, that activates MAP3K12 and a non-canonical MAPK signal transduction pathway that results in enhanced AP-1-mediated transcription of APP (PubMed:28111074).FUNCTION (Microbial infection) Through its interaction with HCV envelope glycoprotein E2, participates in the attachment of HCV to HSPGs and other receptors (LDLr, VLDLr, and SR-B1) on the cell surface and to the assembly, maturation and infectivity of HCV viral particles (PubMed:25122793, PubMed:29695434). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (PubMed:29695434).SUBUNIT Homotetramer (PubMed:8340399). May interact with ABCA1; functionally associated with ABCA1 in the biogenesis of HDLs (PubMed:14754908). May interact with APP/A4 amyloid-beta peptide; the interaction is extremely stable in vitro but its physiological significance is unclear (PubMed:8367470, PubMed:23620513). May interact with MAPT (PubMed:7972031). May interact with MAP2 (PubMed:7891887). In the cerebrospinal fluid, interacts with secreted SORL1 (PubMed:30448281).SUBUNIT (Microbial infection) Interacts with hepatitis C virus (HCV) envelope glycoprotein E2; this interaction is required for HCV infectivity and production.TISSUE SPECIFICITY Produced by several tissues and cell types and mainly found associated with lipid particles in the plasma, the interstitial fluid and lymph (PubMed:25173806). Mainly synthesized by liver hepatocytes (PubMed:25173806). Significant quantities are also produced in brain, mainly by astrocytes and glial cells in the cerebral cortex, but also by neurons in frontal cortex and hippocampus (PubMed:3115992, PubMed:10027417). It is also expressed by cells of the peripheral nervous system (PubMed:10027417, PubMed:25173806). Also expressed by adrenal gland, testis, ovary, skin, kidney, spleen and adipose tissue and macrophages in various tissues (PubMed:25173806).PTM APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma (PubMed:29516132). The extent of glycosylation and sialylation are tissue and context specific (PubMed:29516132). Plasma APOE undergoes desialylation and is less glycosylated and sialylated than the cellular form (PubMed:2498325, PubMed:19838169, PubMed:20511397, PubMed:23234360). Glycosylation is not required for proper expression and secretion (PubMed:2498325). O-glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Ser-314 are minor glycosylation sites compared to Ser-308 (PubMed:19838169, PubMed:23234360).PTM Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold).PTM Phosphorylated by FAM20C in the extracellular medium.PTM Undergoes C-terminal proteolytic processing in neurons. C-terminally truncated APOE has a tendency to form neurotoxic intracellular neurofibrillary tangle-like inclusions in neurons.POLYMORPHISM There are three common APOE alleles identified: APOE*2/APOE-epsilon2/E2, APOE*3/APOE-epsilon3/E3, and APOE*4/APOE-epsilon4/E4. The corresponding ApoE2, ApoE3 and ApoE4 isoforms differentially present Cys and Arg residues at positions 130 and 176. The most common allele in the human population is APOE*3 which sequence is the one displayed in that entry with a Cys at position 130 and an Arg at position 176. Common APOE variants influence lipoprotein metabolism in healthy individuals. Additional variants have been described and are described relative to the three common alleles. Allele APOE*4 is strongly associated with risk for severe COVID-19, increases susceptibility to SARS-CoV-2 infection in neurons and astrocytes (PubMed:33450186).MISCELLANEOUS Binds to and activates LILRB4 on acute myeloid leukemia (AML) cells which leads to suppression of T cell proliferation and promotion of AML cell migration and infiltration.SIMILARITY Belongs to the apolipoprotein A1/A4/E family. UniProt P02649 19 EQUAL 317 EQUAL Reactome DB_ID: 174807 1 chylomicron remnant [extracellular region] chylomicron remnant Reactome DB_ID: 171149 2 cholesterol [ChEBI:16113] cholesterol cholest-5-en-3beta-ol ChEBI 16113 Reactome DB_ID: 174646 1 19 EQUAL 317 EQUAL Reactome DB_ID: 171076 3 cholesteryl ester [ChEBI:17002] cholesteryl ester ChEBI 17002 Reactome DB_ID: 174729 1 ApoB-48:TG:PL complex [extracellular region] ApoB-48:TG:PL complex Reactome DB_ID: 174770 1 UniProt:P04114 APOB APOB APOB FUNCTION Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). Apo B-100 functions as a recognition signal for the cellular binding and internalization of LDL particles by the apoB/E receptor.SUBUNIT Interacts with PCSK9 (PubMed:22580899). Interacts with MTTP (PubMed:26224785, PubMed:27206948). Interacts with AUP1 (PubMed:28183703).INDUCTION Up-regulated in response to enterovirus 71 (EV71) infection (at protein level).PTM Palmitoylated; structural requirement for proper assembly of the hydrophobic core of the lipoprotein particle.POLYMORPHISM Genetic variations in APOB define the low density lipoprotein cholesterol level quantitative trait locus 4 (LDLCQ4) [MIM:615558].DISEASE Defects in APOB associated with defects in other genes (polygenic) can contribute to hypocholesterolemia. UniProt P04114 28 EQUAL 2179 EQUAL Reactome DB_ID: 171066 60 phospholipid [ChEBI:16247] phospholipid ChEBI 16247 Reactome DB_ID: 171126 40 triglyceride [ChEBI:17855] triglyceride ChEBI 17855 Reactome Database ID Release 81 174729 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174729 Reactome R-HSA-174729 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174729.1 Reactome DB_ID: 171126 50 Reactome Database ID Release 81 174807 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174807 Reactome R-HSA-174807 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174807.1 Reactome Database ID Release 81 174792 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174792 Reactome R-HSA-174792 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174792.1 Reactome DB_ID: 174749 1 chylomicron remnant:apoE:LDLR complex [plasma membrane] chylomicron remnant:apoE:LDLR complex Reactome DB_ID: 174659 1 chylomicron remnant:apoE complex [plasma membrane] chylomicron remnant:apoE complex Reactome DB_ID: 174797 1 chylomicron remnant [plasma membrane] chylomicron remnant Reactome DB_ID: 174615 1 19 EQUAL 317 EQUAL Reactome DB_ID: 171076 3 Reactome DB_ID: 171095 2 Reactome DB_ID: 171057 50 Reactome DB_ID: 174666 1 ApoB-48:TG:PL complex [plasma membrane] ApoB-48:TG:PL complex Reactome DB_ID: 174625 1 28 EQUAL 2179 EQUAL Reactome DB_ID: 171142 60 Reactome DB_ID: 171057 40 Reactome Database ID Release 81 174666 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174666 Reactome R-HSA-174666 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174666.1 Reactome Database ID Release 81 174797 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174797 Reactome R-HSA-174797 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174797.1 Reactome DB_ID: 174615 1 19 EQUAL 317 EQUAL Reactome Database ID Release 81 174659 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174659 Reactome R-HSA-174659 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174659.1 Reactome DB_ID: 171053 1 22 EQUAL 860 EQUAL Reactome Database ID Release 81 174749 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174749 Reactome R-HSA-174749 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174749.1 Reactome Database ID Release 81 174657 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174657 Reactome R-HSA-174657 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174657.4 8300609 Pubmed 1994 Secretion-capture role for apolipoprotein E in remnant lipoprotein metabolism involving cell surface heparan sulfate proteoglycans Ji, ZS Fazio, S Lee, YL Mahley, RW J Biol Chem 269:2764-72 ACTIVATION Reactome Database ID Release 81 174591 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174591 Reactome R-HSA-174591 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174591.3 Reactome DB_ID: 174603 extracellular matrix GO 0031012 UniProt:P11150 LIPC LIPC HTGL LIPC FUNCTION Catalyzes the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins, including chylomicrons, intermediate density lipoproteins (IDL), low density lipoproteins (LDL) of large size and high density lipoproteins (HDL), releasing free fatty acids (FFA) and smaller lipoprotein particles (PubMed:7592706, PubMed:8798474, PubMed:12032167, PubMed:26193433). Also exhibits lysophospholipase activity (By similarity). Can hydrolyze both neutral lipid and phospholipid substrates but shows a greater binding affinity for neutral lipid substrates than phospholipid substrates (By similarity). In native LDL, preferentially hydrolyzes the phosphatidylcholine species containing polyunsaturated fatty acids at sn-2 position (PubMed:26193433).ACTIVITY REGULATION Phospholipase A1 and triacylglycerol lipase are inhibited by sphingomyelin.SUBUNIT Homodimer.POLYMORPHISM Genetic variations in LIPC define the high density lipoprotein cholesterol level quantitative trait locus 12 (HDLCQ12) [MIM:612797].POLYMORPHISM Genetic variations in LIPC are associated with non-insulin-dependent diabetes mellitus susceptibility (NIDDM susceptibility) [MIM:125853].SIMILARITY Belongs to the AB hydrolase superfamily. Lipase family. UniProt P11150 23 EQUAL 499 EQUAL chylomicron remnant:apoE:LDLR complex [plasma membrane] => chylomicron remnant:apoE:LDLR complex [clathrin-coated vesicle] (LDLRAP1-dependent) chylomicron remnant:apoE:LDLR complex [plasma membrane] => chylomicron remnant:apoE:LDLR complex [clathrin-coated vesicle] (LDLRAP1-dependent) The molecular details of this event are inferred from those of LDLR-mediated low-density lipoprotein (LDL) endocytosis into coated vesicles (Ji et al. 1994). Authored: D'Eustachio, P, 2007-04-30 14:19:38 Edited: D'Eustachio, P, 2006-02-20 18:35:05 Reactome DB_ID: 174749 1 Reactome DB_ID: 174816 1 clathrin-coated endocytic vesicle membrane GO 0030669 chylomicron remnant:apoE:LDLR complex [clathrin-coated endocytic vesicle membrane] chylomicron remnant:apoE:LDLR complex Reactome DB_ID: 174787 1 chylomicron remnant:apoE complex [clathrin-coated endocytic vesicle membrane] chylomicron remnant:apoE complex Reactome DB_ID: 174651 1 19 EQUAL 317 EQUAL Reactome DB_ID: 174649 1 chylomicron remnant [clathrin-coated endocytic vesicle membrane] chylomicron remnant Reactome DB_ID: 174746 1 ApoB-48:TG:PL complex [clathrin-coated endocytic vesicle membrane] ApoB-48:TG:PL complex Reactome DB_ID: 171138 60 Reactome DB_ID: 174788 1 28 EQUAL 2179 EQUAL Reactome DB_ID: 171068 40 Reactome Database ID Release 81 174746 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174746 Reactome R-HSA-174746 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174746.1 Reactome DB_ID: 171069 2 Reactome DB_ID: 171107 3 Reactome DB_ID: 174651 1 19 EQUAL 317 EQUAL Reactome DB_ID: 171068 50 Reactome Database ID Release 81 174649 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174649 Reactome R-HSA-174649 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174649.1 Reactome Database ID Release 81 174787 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174787 Reactome R-HSA-174787 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174787.1 Reactome DB_ID: 171105 1 22 EQUAL 860 EQUAL Reactome Database ID Release 81 174816 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174816 Reactome R-HSA-174816 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174816.1 Reactome Database ID Release 81 174706 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174706 Reactome R-HSA-174706 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174706.5 ACTIVATION Reactome Database ID Release 81 174774 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174774 Reactome R-HSA-174774 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174774.3 Reactome DB_ID: 171143 UniProt:Q5SW96 LDLRAP1 LDLRAP1 ARH LDLRAP1 FUNCTION Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytosis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity).SUBUNIT Interacts (via PID domain) with LDLR (via NPXY motif) (PubMed:12221107). Binds to soluble clathrin trimers (PubMed:12221107). Interacts with AP2B1; the interaction mediates the association with the AP-2 complex (PubMed:12221107). Interacts with VLDLR (By similarity). Interacts with LRP2 (By similarity).TISSUE SPECIFICITY Expressed at high levels in the kidney, liver, and placenta, with lower levels detectable in brain, heart, muscle, colon, spleen, intestine, lung, and leukocytes.DOMAIN The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1.DOMAIN The PID domain mediates interaction with the NPXY internalization motif of LDLR. UniProt Q5SW96 1 EQUAL 308 EQUAL chylomicron remnant:apoE:LDLR complex [coated vesicle membrane] => chylomicron remnant:apoE:LDLR complex [endosome membrane] chylomicron remnant:apoE:LDLR complex [coated vesicle membrane] => chylomicron remnant:apoE:LDLR complex [endosome membrane] The molecular details of this event are inferred from those of LDLR-mediated low-density lipoprotein (LDL) transport from coated vesicles to endosomes. Authored: D'Eustachio, P, 2007-04-30 14:19:38 Edited: D'Eustachio, P, 2006-02-20 18:35:05 Reactome DB_ID: 174816 1 Reactome DB_ID: 174658 1 endosome membrane GO 0010008 chylomicron remnant:apoE:LDLR complex [endosome membrane] chylomicron remnant:apoE:LDLR complex Reactome DB_ID: 174698 1 chylomicron remnant:apoE complex [endosome membrane] chylomicron remnant:apoE complex Reactome DB_ID: 174795 1 chylomicron remnant [endosome membrane] chylomicron remnant Reactome DB_ID: 174799 1 ApoB-48:TG:PL complex [endosome membrane] ApoB-48:TG:PL complex Reactome DB_ID: 171148 60 Reactome DB_ID: 171093 40 Reactome DB_ID: 174762 1 28 EQUAL 2179 EQUAL Reactome Database ID Release 81 174799 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174799 Reactome R-HSA-174799 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174799.1 Reactome DB_ID: 171135 2 Reactome DB_ID: 171061 3 Reactome DB_ID: 174766 1 19 EQUAL 317 EQUAL Reactome DB_ID: 171093 50 Reactome Database ID Release 81 174795 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174795 Reactome R-HSA-174795 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174795.1 Reactome DB_ID: 174766 1 19 EQUAL 317 EQUAL Reactome Database ID Release 81 174698 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174698 Reactome R-HSA-174698 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174698.1 Reactome DB_ID: 171127 1 22 EQUAL 860 EQUAL Reactome Database ID Release 81 174658 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174658 Reactome R-HSA-174658 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174658.1 Reactome Database ID Release 81 174808 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174808 Reactome R-HSA-174808 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174808.3 chylomicron remnant:apoE:LDLR complex => chylomicron remnant:apoE + LDLR chylomicron remnant:apoE:LDLR complex => chylomicron remnant:apoE + LDLR The molecular details of this event are inferred from the dissociation of the LDL:LDLR complex in the endosome. Authored: D'Eustachio, P, 2007-04-30 14:19:38 Edited: D'Eustachio, P, 2006-02-20 18:35:05 Reactome DB_ID: 174658 1 Reactome DB_ID: 174594 1 endosome lumen GO 0031904 chylomicron remnant:apoE complex [endosome lumen] chylomicron remnant:apoE complex Reactome DB_ID: 174805 1 chylomicron remnant [endosome lumen] chylomicron remnant Reactome DB_ID: 174593 1 ApoB-48:TG:PL complex [endosome lumen] ApoB-48:TG:PL complex Reactome DB_ID: 174716 1 28 EQUAL 2179 EQUAL Reactome DB_ID: 171144 40 Reactome DB_ID: 171150 60 Reactome Database ID Release 81 174593 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174593 Reactome R-HSA-174593 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174593.1 Reactome DB_ID: 171123 3 Reactome DB_ID: 174804 1 19 EQUAL 317 EQUAL Reactome DB_ID: 171144 50 Reactome DB_ID: 171083 2 Reactome Database ID Release 81 174805 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174805 Reactome R-HSA-174805 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174805.1 Reactome DB_ID: 174804 1 19 EQUAL 317 EQUAL Reactome Database ID Release 81 174594 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174594 Reactome R-HSA-174594 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174594.1 Reactome DB_ID: 171127 1 22 EQUAL 860 EQUAL Reactome Database ID Release 81 174624 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174624 Reactome R-HSA-174624 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174624.3 Reactome Database ID Release 81 8964026 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8964026 Reactome R-HSA-8964026 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8964026.1 14748717 Pubmed 2004 Chylomicron metabolism Redgrave, TG Biochem. Soc. Trans. 32:79-82 GO 0034382 GO biological process