Plasma lipoprotein assembly, remodeling, and clearance (Homo sapiens)

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<?xml version="1.0" encoding="UTF-8"?> <Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="Plasma lipoprotein assembly, remodeling, and clearance" Organism="Homo sapiens"> <Comment Source="WikiPathways-description">Because of their hydrophobicity, lipids are found in the extracellular spaces of the human body primarily in the form of lipoprotein complexes. &lt;b&gt;Chylomicrons&lt;/b&gt; form in the small intestine and transport dietary lipids to other tissues in the body. &lt;b&gt;Very low density lipoproteins (VLDL)&lt;/b&gt; form in the liver and transport triacylglycerol synthesized there to other tissues of the body. As they circulate, VLDL are acted on by lipoprotein lipases on the endothelial surfaces of blood vessels, liberating fatty acids and glycerol to be taken up by tissues and converting the VLDL first to &lt;b&gt;intermediate density lipoproteins (IDL)&lt;/b&gt; and then to &lt;b&gt;low density lipoproteins (LDL)&lt;/b&gt;. IDL and LDL are cleared from the circulation via a specific cell surface receptor, found in the body primarily on the surfaces of liver cells. &lt;b&gt;High density lipoprotein (HDL)&lt;/b&gt; particles, initially formed primarily by the liver, shuttle several kinds of lipids between tissues and other lipoproteins. Notably, they are responsible for the so-called reverse transport of cholesterol from peripheral tissues to LDL for return to the liver.&lt;p&gt;Three aspects of lipoprotein function are currently annotated in Reactome: &lt;b&gt;chylomicron-mediated lipid transport&lt;/b&gt;, &lt;b&gt;LDL endocytosis and degradation&lt;/b&gt;, and &lt;b&gt;HDL-mediated lipid transport&lt;/b&gt;, each divided into assembly, remodeling, and clearance subpathways. View original pathway at:[http://www.reactome.org/PathwayBrowser/#DIAGRAM=174824 Reactome].</Comment> <Comment Source="Reactome-Converter">Pathway is converted from Reactome ID: 174824</Comment> <Comment Source="Reactome-version">Reactome version: 65</Comment> <Comment Source="Reactome Author">Reactome Author: D'Eustachio, Peter</Comment> <Attribute Key="reactome_id" Value="174824" /> <Graphics BoardWidth="4055.0" BoardHeight="2512.0" /> <DataNode TextLabel="TAGs " GraphId="a0072" Type="Metabolite" GroupRef="ccab5"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-171131" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1080.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="a016f" Type="Metabolite" GroupRef="ad7ae"> <Attribute Key="cellular_location" 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Database="Uniprot-TrEMBL" ID="P63010" /> </DataNode> <DataNode TextLabel="LSR " GraphId="a744b" Type="Protein" GroupRef="db61c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8933254" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="1780.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q86X29" /> </DataNode> <DataNode TextLabel="SOAT2 " GraphId="a788f" Type="Protein" GroupRef="c76ec"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-8876694" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O75908" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="a79a6" Type="Metabolite" GroupRef="bb72d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349645" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="2620.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="a7d9a" Type="Protein" GroupRef="c8924"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="240.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="PL " GraphId="a8201" Type="Metabolite" GroupRef="f2ca5"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-174630" /> <Attribute Key="copies_num" Value="60" /> <Graphics CenterX="100.0" CenterY="1672.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="PL " GraphId="a8294" Type="Metabolite" GroupRef="e9db1"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="182" /> <Graphics CenterX="2340.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="a86d1" Type="Metabolite" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="240.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="a8af6" Type="Protein" GroupRef="c4639"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="2340.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="a8fdf" Type="Protein" GroupRef="b6e25"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266083" /> <Attribute Key="copies_num" Value="12" /> <Graphics CenterX="1220.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="PL " GraphId="a9197" Type="Metabolite" GroupRef="f801c"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-171108" /> <Attribute Key="copies_num" Value="2858" /> <Graphics CenterX="1920.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="PL" GraphId="a9775" Type="Metabolite"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Graphics CenterX="2373.0" CenterY="184.0" Width="30.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="PCSK5" GraphId="a97e0" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="808.0" CenterY="379.0" Width="46.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q92824" /> </DataNode> <DataNode TextLabel="PL " GraphId="a98ee" Type="Metabolite" GroupRef="efecd"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174769" /> <Attribute Key="copies_num" Value="183" /> <Graphics CenterX="940.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="ANGPTL4" GraphId="a9b01" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="950.0" CenterY="310.0" Width="64.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9BY76" /> </DataNode> <DataNode TextLabel="SCARB1-2" GraphId="a9b07" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3881.0" CenterY="1208.5" Width="72.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8WTV0-2" /> </DataNode> <DataNode TextLabel="ZDHHC8" GraphId="a9f77" Type="Protein"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="2926.0" CenterY="269.0" Width="60.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9ULC8" /> </DataNode> <DataNode TextLabel="LIPC" GraphId="aa051" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular matrix" /> <Graphics CenterX="1714.0" CenterY="893.0" Width="46.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11150" /> </DataNode> <DataNode TextLabel="LDL" GraphId="aa0a7" Type="Complex"> <Comment Source="Reactome">LDL (low density lipoproteins) are complexes of a single molecule of apoprotein B-100 (apoB-100) non-covalently associated with triacylglycerol, free cholesterol, cholesterol esters, and phospholipids. LDL complexes contain single molecules of apoB-100, but their content of lipids is variable (Chapman et al. 1988; Mateu et al. 1972; Tardieu et al. 1976). High levels of LDL in the blood are strongly correlated with increased risk of atherosclerosis, and recent studies have raised the possibility that this risk is further increased in individuals whose blood LDL population is enriched in high-density (low lipid content) LDL complexes (Rizzo and Berneis 2006). The LDL complex annotated here contains an average lipid composition.</Comment> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Graphics CenterX="2406.0" CenterY="1106.0" Width="30.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8876367" /> </DataNode> <DataNode TextLabel="PL " GraphId="aa0ce" Type="Metabolite" GroupRef="ad7ae"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266348" /> <Attribute Key="copies_num" Value="182" /> <Graphics CenterX="1360.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="aa168" Type="Metabolite" GroupRef="e8b10"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-349649" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="2340.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="TAG" GraphId="aa1d8" Type="Metabolite"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Graphics CenterX="2359.0" CenterY="147.0" Width="42.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="4xPALM-C-ABCA1&#xA;tetramer" GraphId="aa304" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="3081.5" CenterY="207.0" Width="123.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-5682067" /> </DataNode> <DataNode TextLabel="CETP " GraphId="aa30c" Type="Protein" GroupRef="c2ef8"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349410" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1500.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11597" /> </DataNode> <DataNode TextLabel="CREB3L3(1-?)" GraphId="aa465" Type="Protein"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Graphics CenterX="234.0" CenterY="209.5" Width="60.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q68CJ9" /> </DataNode> <DataNode TextLabel="APOA1(25-266)" GraphId="aa6ab" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3952.0" CenterY="615.0" Width="66.0" Height="42.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="PL " GraphId="aa784" Type="Metabolite" GroupRef="e344a"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="182" /> <Graphics CenterX="1220.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="aa7d9" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3926.5" CenterY="538.0" Width="53.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="LCAT:spherical HDL&#xA;complex" GraphId="aa88d" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3551.5" CenterY="948.0" Width="91.0" Height="50.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-266308" /> </DataNode> <DataNode TextLabel="TAGs" GraphId="aaa43" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3742.0" CenterY="938.0" Width="48.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="PL " GraphId="aaabb" Type="Metabolite" GroupRef="c2ef8"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349410" /> <Attribute Key="copies_num" Value="142" /> <Graphics CenterX="1500.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="A2M " GraphId="aacf2" Type="Protein" GroupRef="d1d54"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-158255" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="520.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01023" /> </DataNode> <DataNode TextLabel="chylomicron&#xA;remnant:apoE:LDLR&#xA;complex" GraphId="ab012" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="1598.0" CenterY="882.0" Width="90.0" Height="64.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174749" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="ab080" Type="Metabolite" GroupRef="f36a2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266308" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="1360.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="ab29e" Type="Metabolite"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3788.5" CenterY="1600.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="aba50" Type="Metabolite" GroupRef="b2a62"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-174816" /> <Attribute Key="copies_num" Value="150" /> <Graphics CenterX="1500.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="abc84" Type="Protein" GroupRef="db61c"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933254" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="1780.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="PL " GraphId="abdb6" Type="Metabolite" GroupRef="c8924"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="182" /> <Graphics CenterX="240.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="pre-beta HDL" GraphId="ac1be" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3843.5" CenterY="359.0" Width="99.0" Height="26.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-349645" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="ac226" Type="Protein" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="ADP" GraphId="ac29a" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3299.5" CenterY="258.0" Width="41.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16761" /> </DataNode> <DataNode TextLabel="cholesterol " GraphId="ac302" Type="Metabolite" GroupRef="f801c"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-171108" /> <Attribute Key="copies_num" Value="670" /> <Graphics CenterX="1920.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="ABCG1 " GraphId="ac545" Type="Protein" GroupRef="f9248"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-194222" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1220.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P45844" /> </DataNode> <DataNode TextLabel="LSR " GraphId="ad2e8" Type="Protein" GroupRef="d1124"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8933252" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="1920.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q86X29" /> </DataNode> <DataNode TextLabel="4xPALM-C-p-2S-ABCA1 " GraphId="ad48c" Type="Protein" GroupRef="d22f8"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-5682107" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="520.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95477" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="ad6b1" Type="Metabolite" GroupRef="cd846"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174791" /> <Attribute Key="copies_num" Value="202" /> <Graphics CenterX="100.0" CenterY="2312.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="ad999" Type="Metabolite" GroupRef="d7762"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8866325" /> <Attribute Key="copies_num" Value="2187" /> <Graphics CenterX="380.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="NR1H3 " GraphId="addb5" Type="Protein" GroupRef="e3e00"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Attribute Key="complex_id" Value="R-HSA-8854954" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q13133" /> </DataNode> <DataNode TextLabel="APOE " GraphId="ae0ab" Type="Protein" GroupRef="fd9be"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174807" /> <Attribute Key="copies_num" Value="149" /> <Graphics CenterX="940.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="LMF2 " GraphId="ae30b" Type="Protein" GroupRef="dda44"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-6785148" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9BU23" /> </DataNode> <DataNode TextLabel="AP2A2(1-939) " GraphId="ae396" Type="Protein" GroupRef="cee8c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855134" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O94973" /> </DataNode> <DataNode TextLabel="Heparins" GraphId="ae7f2" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="835.0" CenterY="533.0" Width="70.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:24505" /> </DataNode> <DataNode TextLabel="LIPA-degraded LDL" GraphId="ae858" Type="Complex"> <Comment Source="Reactome">LDL (low density lipoproteins) are complexes of a single molecule of apoprotein B-100 (apoB-100) non-covalently associated with triacylglycerol, free cholesterol, cholesterol esters, and phospholipids. LDL complexes contain single molecules of apoB-100, but their content of lipids is variable (Chapman et al. 1988; Mateu et al. 1972; Tardieu et al. 1976). High levels of LDL in the blood are strongly correlated with increased risk of atherosclerosis, and recent studies have raised the possibility that this risk is further increased in individuals whose blood LDL population is enriched in high-density (low lipid content) LDL complexes (Rizzo and Berneis 2006). The LDL complex annotated here contains an average lipid composition.</Comment> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Graphics CenterX="2218.5" CenterY="1106.0" Width="71.0" Height="46.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8876365" /> </DataNode> <DataNode TextLabel="torcetrapib " GraphId="ae8ee" Type="Metabolite" GroupRef="c2ef8"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349410" /> <Attribute Key="copies_num" Value="364" /> <Graphics CenterX="1500.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:49203" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="aec11" Type="Metabolite" GroupRef="b9853"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266340" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1080.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOE " GraphId="aecab" Type="Protein" GroupRef="b2a62"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-174816" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1500.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="APOA2(24-100) " GraphId="aee8c" Type="Protein" GroupRef="c0ffc"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174626" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="100.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02652" /> </DataNode> <DataNode TextLabel="CLTC " GraphId="aef18" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2200.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q00610" /> </DataNode> <DataNode TextLabel="APOE" GraphId="af24a" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3343.5" CenterY="813.0" Width="45.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="NR1H2 " GraphId="af331" Type="Protein" GroupRef="e3e00"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Attribute Key="complex_id" Value="R-HSA-8854954" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P55055" /> </DataNode> <DataNode TextLabel="ABCA1 tetramer" GraphId="af7c7" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="2811.0" CenterY="207.0" Width="76.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-5682087" /> </DataNode> <DataNode TextLabel="H2O" GraphId="af996" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3540.5" CenterY="208.0" Width="43.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15377" /> </DataNode> <DataNode TextLabel="LDLR" GraphId="afa39" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="1595.5" CenterY="804.0" Width="45.0" Height="26.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="4xPALM-C-p-2S-ABCA1&#xA;tetramer:APOA1" GraphId="afb36" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3492.5" CenterY="318.5" Width="105.0" Height="51.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-5682094" /> </DataNode> <DataNode TextLabel="CLTA " GraphId="b003c" Type="Protein" GroupRef="aa20d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="2060.0" CenterY="2372.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P09496" /> </DataNode> <DataNode TextLabel="AP2A2(1-939) " GraphId="b005c" Type="Protein" GroupRef="c5c02"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855135" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2620.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O94973" /> </DataNode> <DataNode TextLabel="AP2A2(1-939) " GraphId="b0481" Type="Protein" GroupRef="a8f2d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2392.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O94973" /> </DataNode> <DataNode TextLabel="VLDLR" GraphId="b049b" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="1876.5" CenterY="537.5" Width="57.0" Height="23.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P98155" /> </DataNode> <DataNode TextLabel="LCAT:discoidal HDL&#xA;complex" GraphId="b04b2" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3762.5" CenterY="740.5" Width="91.0" Height="47.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-264684" /> </DataNode> <DataNode TextLabel="TAG " GraphId="b0920" Type="Metabolite" GroupRef="c815b"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784871" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="Clathrin:AP-2&#xA;complex" GraphId="b12db" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3233.0" CenterY="1150.0" Width="88.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-177505" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="b14bf" Type="Metabolite" GroupRef="db61c"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933254" /> <Attribute Key="copies_num" Value="672" /> <Graphics CenterX="1780.0" CenterY="2252.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="b16cf" Type="Metabolite" GroupRef="cd76e"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-171100" /> <Attribute Key="copies_num" Value="670" /> <Graphics CenterX="1920.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CLTA " GraphId="b1ab1" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="2200.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P09496" /> </DataNode> <DataNode TextLabel="PCSK9 " GraphId="b1fb8" Type="Protein" GroupRef="c5c02"> <Attribute Key="cellular_location" Value="lysosomal membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855135" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2620.0" CenterY="1832.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8NBP7" /> </DataNode> <DataNode TextLabel="H2O" GraphId="b21bb" Type="Metabolite"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Graphics CenterX="2390.5" CenterY="1038.0" Width="43.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15377" /> </DataNode> <DataNode TextLabel="APOC3 " GraphId="b23b7" Type="Protein" GroupRef="d3c01"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="240.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02656" /> </DataNode> <DataNode TextLabel="H2O" GraphId="b28c2" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3389.0" CenterY="574.0" Width="48.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15377" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="b2a6b" Type="Metabolite" GroupRef="c2ef8"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349410" /> <Attribute Key="copies_num" Value="364" /> <Graphics CenterX="1500.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="chylomicron&#xA;remnant:apoE:LDLR&#xA;complex" GraphId="b37cc" Type="Complex"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Graphics CenterX="1479.5" CenterY="956.5" Width="107.0" Height="55.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174816" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="b3c05" Type="Metabolite" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="200" /> <Graphics CenterX="240.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="PL " GraphId="b4058" Type="Metabolite" GroupRef="d7e28"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="182" /> <Graphics CenterX="1220.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="ATP" GraphId="b41ae" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3354.0" CenterY="665.0" Width="48.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15422" /> </DataNode> <DataNode TextLabel="AP2B1 " GraphId="b44a7" Type="Protein" GroupRef="e010b"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-2130671" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P63010" /> </DataNode> <DataNode TextLabel="cholesterol " GraphId="b44d8" Type="Metabolite" GroupRef="cf5eb"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-174594" /> <Attribute Key="copies_num" Value="151" /> <Graphics CenterX="1640.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="LDLR" GraphId="b47db" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2657.5" CenterY="1009.0" Width="45.0" Height="26.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="CREB3L3" GraphId="b4814" Type="Protein"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="413.5" CenterY="119.0" Width="61.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q68CJ9" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="b4826" Type="Metabolite"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3713.5" CenterY="311.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="TAGs" GraphId="b4b88" Type="Metabolite"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="1306.0" CenterY="58.0" Width="48.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOA4 " GraphId="b4bc2" Type="Protein" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="149" /> <Graphics CenterX="800.0" CenterY="2292.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06727" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="b4cca" Type="Protein" GroupRef="efecd"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174769" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="940.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="PL " GraphId="b4de1" Type="Metabolite" GroupRef="d7762"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8866325" /> <Attribute Key="copies_num" Value="1288" /> <Graphics CenterX="380.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOE " GraphId="b4e62" Type="Protein" GroupRef="d3c01"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="240.0" CenterY="1832.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="b4fee" Type="Metabolite" GroupRef="fd9be"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174807" /> <Attribute Key="copies_num" Value="150" /> <Graphics CenterX="940.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOA1(19-266)" GraphId="b53c8" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3163.0" CenterY="414.0" Width="68.0" Height="38.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="APOC1 " GraphId="b561e" Type="Protein" GroupRef="b415d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8854464" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1640.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02654" /> </DataNode> <DataNode TextLabel="PL " GraphId="b5aeb" Type="Metabolite" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="60" /> <Graphics CenterX="240.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="PL " GraphId="b5b9f" Type="Metabolite" GroupRef="b1640"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-264684" /> <Attribute Key="copies_num" Value="35" /> <Graphics CenterX="1220.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOC2" GraphId="b5c9a" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1237.5" CenterY="523.5" Width="55.0" Height="23.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02655" /> </DataNode> <DataNode TextLabel="APOA1(25-266)" GraphId="b5ee4" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3364.0" CenterY="413.0" Width="66.0" Height="42.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="CLTA " GraphId="b61ca" Type="Protein" GroupRef="cee8c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855134" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="2480.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P09496" /> </DataNode> <DataNode TextLabel="HSPG:LPL dimer" GraphId="b6366" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="711.0" CenterY="220.0" Width="84.0" Height="40.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8867477" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="b674a" Type="Metabolite" GroupRef="c178b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855875" /> <Attribute Key="copies_num" Value="680" /> <Graphics CenterX="520.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOC1 " GraphId="b69c6" Type="Protein" GroupRef="d9e63"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933291" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="1780.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02654" /> </DataNode> <DataNode TextLabel="NR1H2,NR1H3" GraphId="b6a03" Type="Complex"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Graphics CenterX="3176.5" CenterY="1323.5" Width="67.0" Height="39.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8854954" /> </DataNode> <DataNode TextLabel="4xPALM-C-p-2S-ABCA1&#xA;tetramer" GraphId="b6a22" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3355.0" CenterY="319.0" Width="114.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-5682107" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="b6cc4" Type="Metabolite" GroupRef="b415d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8854464" /> <Attribute Key="copies_num" Value="829" /> <Graphics CenterX="1640.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="CoA-SH" GraphId="b6d81" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3015.0" CenterY="271.0" Width="64.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15346" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="b70c1" Type="Protein" GroupRef="c815b"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-6784871" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="APOE " GraphId="b70f9" Type="Protein" GroupRef="d7e28"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="1220.0" CenterY="2252.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="LDLR " GraphId="b7221" Type="Protein" GroupRef="e6276"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784730" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="LSR trimer" GraphId="b7295" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2569.0" CenterY="794.5" Width="60.0" Height="37.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8933252" /> </DataNode> <DataNode TextLabel="HSPG " GraphId="b73b5" Type="Metabolite" GroupRef="af498"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8857969" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:24499" /> </DataNode> <DataNode TextLabel="Heparins " GraphId="b7533" Type="Metabolite" GroupRef="ef513"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6785208" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:24505" /> </DataNode> <DataNode TextLabel="AP2S1 " GraphId="b75ff" Type="Protein" GroupRef="a8f2d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2352.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P53680" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="b7703" Type="Metabolite"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="1529.5" CenterY="196.0" Width="51.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="b78f8" Type="Protein" GroupRef="aa890"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266339" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1080.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="PCSK9" GraphId="b7c6c" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3314.5" CenterY="1284.0" Width="53.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8NBP7" /> </DataNode> <DataNode TextLabel="PL " GraphId="b7d83" Type="Metabolite" GroupRef="ea96e"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876367" /> <Attribute Key="copies_num" Value="1359" /> <Graphics CenterX="2060.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="LDLR " GraphId="b81b3" Type="Protein" GroupRef="b2a62"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-174816" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1500.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="CUBN " GraphId="b81f0" Type="Protein" GroupRef="a2c7a"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-264851" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O60494" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="b84b5" Type="Metabolite" GroupRef="e75f1"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174749" /> <Attribute Key="copies_num" Value="153" /> <Graphics CenterX="1500.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="spherical&#xA;HDL:apoC-II:apoC-III:apoE" GraphId="b86aa" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3430.0" CenterY="929.0" Width="96.0" Height="52.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174643" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="b88da" Type="Metabolite"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="2066.5" CenterY="879.0" Width="51.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOC2 " GraphId="b8d1a" Type="Protein" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="240.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02655" /> </DataNode> <DataNode TextLabel="APOC4 " GraphId="b8e54" Type="Protein" GroupRef="d9e63"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933291" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="1780.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P55056" /> </DataNode> <DataNode TextLabel="LMF1 " GraphId="b91c4" Type="Protein" GroupRef="c2e2b"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-6785173" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96S06" /> </DataNode> <DataNode TextLabel="spherical HDL" GraphId="b96ca" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3832.0" CenterY="1108.0" Width="76.0" Height="40.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-265523" /> </DataNode> <DataNode TextLabel="APOBR dimer:VLDL" GraphId="b981e" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2273.5" CenterY="538.0" Width="79.0" Height="38.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8856140" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="b9cc4" Type="Metabolite" GroupRef="c8924"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="43" /> <Graphics CenterX="240.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOA1(25-267)" GraphId="b9e33" Type="Protein"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="1453.5" CenterY="196.5" Width="65.0" Height="31.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="LPL" GraphId="b9e41" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="858.5" CenterY="164.0" Width="29.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06858" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="ba4b2" Type="Metabolite" GroupRef="e9db1"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="2340.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="ba624" Type="Metabolite"> <Attribute Key="cellular_location" Value="transport vesicle membrane" /> <Graphics CenterX="2078.5" CenterY="1062.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOC3 " GraphId="ba8ec" Type="Protein" GroupRef="efecd"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174769" /> <Attribute Key="copies_num" Value="361" /> <Graphics CenterX="940.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02656" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="ba94d" Type="Metabolite" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="202" /> <Graphics CenterX="240.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="baabb" Type="Metabolite" GroupRef="d7762"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8866325" /> <Attribute Key="copies_num" Value="829" /> <Graphics CenterX="380.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="PLTP-1 " GraphId="bad0d" Type="Protein" GroupRef="ee17d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-194227" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1360.0" CenterY="1832.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P55058-1" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="bb728" Type="Protein" GroupRef="e344a"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="1220.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="bb82e" Type="Metabolite" GroupRef="fd9be"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174807" /> <Attribute Key="copies_num" Value="149" /> <Graphics CenterX="940.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="bbf2b" Type="Protein" GroupRef="b9478"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Attribute Key="complex_id" Value="R-HSA-8866319" /> <Attribute Key="copies_num" Value="2189" /> <Graphics CenterX="380.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="bbff0" Type="Metabolite" GroupRef="fd9be"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174807" /> <Attribute Key="copies_num" Value="152" /> <Graphics CenterX="940.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="bc880" Type="Protein" GroupRef="e3b46"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855688" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="1360.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="ABCA1 " GraphId="bcc9d" Type="Protein" GroupRef="b0b00"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-5682087" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="520.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95477" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="bcd24" Type="Metabolite" GroupRef="aa890"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266339" /> <Attribute Key="copies_num" Value="2171" /> <Graphics CenterX="1080.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="FGF21 gene " GraphId="bce12" Type="Protein" GroupRef="c47fc"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Attribute Key="complex_id" Value="R-HSA-6784668" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2372.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Ensembl" ID="ENSG00000105550" /> </DataNode> <DataNode TextLabel="BMP1-3:Zn2+" GraphId="bd263" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3250.0" CenterY="462.5" Width="68.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-264759" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="bd37b" Type="Metabolite" GroupRef="efecd"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174769" /> <Attribute Key="copies_num" Value="361" /> <Graphics CenterX="940.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="spherical HDL" GraphId="bdee5" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3966.5" CenterY="1244.5" Width="67.0" Height="35.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-265523" /> </DataNode> <DataNode TextLabel="VLDL:PCSK9:Clathrin:AP2" GraphId="bdf3d" Type="Complex"> <Attribute Key="cellular_location" Value="lysosomal membrane" /> <Graphics CenterX="3055.5" CenterY="1274.5" Width="79.0" Height="53.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8855135" /> </DataNode> <DataNode TextLabel="cholesterol esters " GraphId="be21a" Type="Metabolite" GroupRef="cf5eb"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-174594" /> <Attribute Key="copies_num" Value="153" /> <Graphics CenterX="1640.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOC1 " GraphId="beac7" Type="Protein" GroupRef="c178b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855875" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02654" /> </DataNode> <DataNode TextLabel="LDLRAP1" GraphId="bebf7" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2658.0" CenterY="952.0" Width="74.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q5SW96" /> </DataNode> <DataNode TextLabel="FURIN,PCSK6" GraphId="bf040" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="889.5" CenterY="371.0" Width="65.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6784618" /> </DataNode> <DataNode TextLabel="PCSK9 " GraphId="bf4f8" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2200.0" CenterY="1832.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8NBP7" /> </DataNode> <DataNode TextLabel="AP2B1 " GraphId="bf611" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P63010" /> </DataNode> <DataNode TextLabel="ANGPTL8 " GraphId="bf6c4" Type="Protein" GroupRef="bdd41"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6784846" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q6UXH0" /> </DataNode> <DataNode TextLabel="CHEST" GraphId="bfb1d" Type="Metabolite"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="1592.5" CenterY="192.0" Width="53.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="TAG " GraphId="bfccc" Type="Metabolite" GroupRef="a61cf"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Attribute Key="complex_id" Value="R-HSA-8866311" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="bfdf5" Type="Metabolite" GroupRef="e9db1"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="43" /> <Graphics CenterX="2340.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="cholesterol esters " GraphId="bff8b" Type="Metabolite" GroupRef="ea96e"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876367" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="2060.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOC4 " GraphId="c0021" Type="Protein" GroupRef="c178b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855875" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P55056" /> </DataNode> <DataNode TextLabel="LDLR " GraphId="c02f6" Type="Protein" GroupRef="fa242"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-171056" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1920.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="chylomicron&#xA;remnant:apoE&#xA;complex" GraphId="c04e0" Type="Complex"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Graphics CenterX="1479.0" CenterY="1194.0" Width="96.0" Height="50.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174594" /> </DataNode> <DataNode TextLabel="NPC1" GraphId="c04f6" Type="Protein"> <Attribute Key="cellular_location" Value="lysosomal membrane" /> <Graphics CenterX="2171.5" CenterY="876.0" Width="41.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O15118" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="c090d" Type="Metabolite" GroupRef="a601d"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876365" /> <Attribute Key="copies_num" Value="1528" /> <Graphics CenterX="2060.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="AP2A1 " GraphId="c10a0" Type="Protein" GroupRef="a8f2d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2372.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95782" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="c1234" Type="Metabolite" GroupRef="d605b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349645" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="660.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="PL" GraphId="c15ea" Type="Metabolite"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3503.0" CenterY="690.0" Width="30.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="c207e" Type="Metabolite" GroupRef="aa890"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266339" /> <Attribute Key="copies_num" Value="670" /> <Graphics CenterX="1080.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="LCAT " GraphId="c2089" Type="Protein" GroupRef="b1640"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-264684" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1220.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04180" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="c25d8" Type="Metabolite" GroupRef="b415d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8854464" /> <Attribute Key="copies_num" Value="2187" /> <Graphics CenterX="1640.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="H2O" GraphId="c2df2" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3766.5" CenterY="980.0" Width="45.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15377" /> </DataNode> <DataNode TextLabel="PL " GraphId="c312d" Type="Metabolite" GroupRef="c0ffc"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174626" /> <Attribute Key="copies_num" Value="60" /> <Graphics CenterX="100.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="VLDL" GraphId="c320e" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2287.0" CenterY="436.0" Width="38.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8855875" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="c3235" Type="Metabolite" GroupRef="d7762"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8866325" /> <Attribute Key="copies_num" Value="680" /> <Graphics CenterX="380.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="c351a" Type="Protein" GroupRef="d605b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349645" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="660.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="c36a3" Type="Protein" GroupRef="d4013"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-216752" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="520.0" CenterY="2432.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="c3e07" Type="Protein" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="c3f49" Type="Metabolite" GroupRef="a92fc"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174792" /> <Attribute Key="copies_num" Value="150" /> <Graphics CenterX="940.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="apoA-I:CUBN:AMN&#xA;complex" GraphId="c3f76" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3624.5" CenterY="1363.0" Width="99.0" Height="38.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-264851" /> </DataNode> <DataNode TextLabel="Clathrin:AP2 complex" GraphId="c40b0" Type="Complex"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Graphics CenterX="2229.0" CenterY="1318.5" Width="90.0" Height="37.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-2130671" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="c422b" Type="Metabolite" GroupRef="c8924"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="240.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="LIPC dimer:LMF1,2" GraphId="c441e" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="606.5" CenterY="367.0" Width="75.0" Height="38.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6785173" /> </DataNode> <DataNode TextLabel="PL" GraphId="c4543" Type="Metabolite"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3846.0" CenterY="1600.0" Width="30.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="PL " GraphId="c4664" Type="Metabolite" GroupRef="d605b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349645" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="660.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="AMN " GraphId="c4935" Type="Protein" GroupRef="a2c7a"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-264851" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9BXJ7" /> </DataNode> <DataNode TextLabel="MYLIP dimer" GraphId="c52d0" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3180.0" CenterY="1378.0" Width="62.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8855129" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="c5668" Type="Metabolite" GroupRef="d9e63"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933291" /> <Attribute Key="copies_num" Value="2189" /> <Graphics CenterX="1780.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="c59a0" Type="Metabolite"> <Attribute Key="cellular_location" Value="transport vesicle membrane" /> <Graphics CenterX="3335.5" CenterY="585.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="cholesterol " GraphId="c5af0" Type="Metabolite" GroupRef="e41b5"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-174658" /> <Attribute Key="copies_num" Value="151" /> <Graphics CenterX="1640.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="c5cbe" Type="Protein" GroupRef="a82b2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-176866" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1080.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="APOE " GraphId="c5e8c" Type="Protein" GroupRef="e75f1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-174749" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1500.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="PRKACA " GraphId="c6037" Type="Protein" GroupRef="d9479"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-111920" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="2252.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P17612" /> </DataNode> <DataNode TextLabel="HDLBP" GraphId="c6265" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3881.0" CenterY="1154.0" Width="76.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q00341" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="c64e1" Type="Metabolite" GroupRef="efecd"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174769" /> <Attribute Key="copies_num" Value="342" /> <Graphics CenterX="940.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="c67e9" Type="Metabolite" GroupRef="c0ffc"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174626" /> <Attribute Key="copies_num" Value="200" /> <Graphics CenterX="100.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="TAG " GraphId="c6867" Type="Metabolite" GroupRef="b9478"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Attribute Key="complex_id" Value="R-HSA-8866319" /> <Attribute Key="copies_num" Value="1361" /> <Graphics CenterX="380.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="c737c" Type="Protein" GroupRef="fa242"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-171056" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1920.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="NPC2 " GraphId="c73e1" Type="Protein" GroupRef="be863"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876460" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P61916" /> </DataNode> <DataNode TextLabel="APOB(28-2179)" GraphId="c753b" Type="Protein"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="1179.0" CenterY="58.0" Width="88.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="c7743" Type="Metabolite" GroupRef="c2ef8"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349410" /> <Attribute Key="copies_num" Value="163" /> <Graphics CenterX="1500.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="AP2A2(1-939) " GraphId="c7d05" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O94973" /> </DataNode> <DataNode TextLabel="CIDEC gene " GraphId="c81a2" Type="Protein" GroupRef="c47fc"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Attribute Key="complex_id" Value="R-HSA-6784668" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2352.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Ensembl" ID="ENSG00000187288" /> </DataNode> <DataNode TextLabel="LMF1,2" GraphId="c8603" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="606.0" CenterY="275.0" Width="52.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6785148" /> </DataNode> <DataNode TextLabel="AP2M1 " GraphId="c87fc" Type="Protein" GroupRef="e010b"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-2130671" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96CW1" /> </DataNode> <DataNode TextLabel="APOE " GraphId="c89ba" Type="Protein" GroupRef="a92fc"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174792" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="940.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="GPIHBP1 " GraphId="c8a28" Type="Protein" GroupRef="af498"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8857969" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8IV16" /> </DataNode> <DataNode TextLabel="APOC2 " GraphId="c8e70" Type="Protein" GroupRef="efecd"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174769" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="940.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02655" /> </DataNode> <DataNode TextLabel="CLTA " GraphId="c8f57" Type="Protein" GroupRef="a8f2d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="2480.0" CenterY="2412.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P09496" /> </DataNode> <DataNode TextLabel="APOC2 " GraphId="c8f6e" Type="Protein" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="149" /> <Graphics CenterX="800.0" CenterY="2332.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02655" /> </DataNode> <DataNode TextLabel="ADP" GraphId="c9026" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3474.0" CenterY="590.5" Width="48.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16761" /> </DataNode> <DataNode TextLabel="cholesterol esters " GraphId="c9047" Type="Metabolite" GroupRef="dd849"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-171082" /> <Attribute Key="copies_num" Value="2169" /> <Graphics CenterX="1920.0" CenterY="2272.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOC3 " GraphId="c914e" Type="Protein" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="240.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02656" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="c99c0" Type="Metabolite" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="150" /> <Graphics CenterX="800.0" CenterY="2392.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOA4 " GraphId="c9a3e" Type="Protein" GroupRef="dd6ab"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-6784718" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06727" /> </DataNode> <DataNode TextLabel="LSR " GraphId="c9b75" Type="Protein" GroupRef="d9e63"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8933291" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="1780.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q86X29" /> </DataNode> <DataNode TextLabel="NPC2" GraphId="c9d5f" Type="Protein"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Graphics CenterX="2279.5" CenterY="995.0" Width="51.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P61916" /> </DataNode> <DataNode TextLabel="APOA2(24-100) " GraphId="ca1aa" Type="Protein" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="149" /> <Graphics CenterX="800.0" CenterY="2312.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02652" /> </DataNode> <DataNode TextLabel="spherical HDL" GraphId="ca26c" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3475.5" CenterY="752.5" Width="75.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-265523" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="ca57b" Type="Metabolite" GroupRef="b9478"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Attribute Key="complex_id" Value="R-HSA-8866319" /> <Attribute Key="copies_num" Value="1510" /> <Graphics CenterX="380.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="LIPC dimer" GraphId="ca814" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="533.0" CenterY="292.0" Width="60.0" Height="34.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6785190" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="ca94a" Type="Metabolite" GroupRef="a82b2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-176866" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1080.0" CenterY="2252.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="cab39" Type="Metabolite" GroupRef="a92fc"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174792" /> <Attribute Key="copies_num" Value="151" /> <Graphics CenterX="940.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="cabe3" Type="Protein" GroupRef="e8b10"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-349649" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="2340.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="4xPALM-C-ABCA1 " GraphId="cafee" Type="Protein" GroupRef="d7a11"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-5682067" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="520.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95477" /> </DataNode> <DataNode TextLabel="AP2A1 " GraphId="cb026" Type="Protein" GroupRef="e010b"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-2130671" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95782" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="cb23a" Type="Metabolite"> <Attribute Key="cellular_location" Value="transport vesicle membrane" /> <Graphics CenterX="3592.5" CenterY="175.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="PL " GraphId="cb3f6" Type="Metabolite" GroupRef="dd849"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-171082" /> <Attribute Key="copies_num" Value="2858" /> <Graphics CenterX="1920.0" CenterY="2292.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="AP2A1 " GraphId="cb576" Type="Protein" GroupRef="cee8c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855134" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95782" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="cb592" Type="Protein" GroupRef="cf5eb"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-174594" /> <Attribute Key="copies_num" Value="61" /> <Graphics CenterX="1640.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="PL " GraphId="cbc40" Type="Metabolite" GroupRef="e75f1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-174749" /> <Attribute Key="copies_num" Value="61" /> <Graphics CenterX="1500.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="cbc8e" Type="Metabolite" GroupRef="a601d"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876365" /> <Attribute Key="copies_num" Value="670" /> <Graphics CenterX="2060.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="MBTPS1 " GraphId="cbe1c" Type="Protein" GroupRef="ef8e8"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784711" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q14703" /> </DataNode> <DataNode TextLabel="PCSK9:LDLR:Clathrin:AP2" GraphId="cbfa8" Type="Complex"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Graphics CenterX="2397.0" CenterY="1319.5" Width="94.0" Height="37.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6784728" /> </DataNode> <DataNode TextLabel="cholesterol " GraphId="cc668" Type="Metabolite" GroupRef="dd849"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-171082" /> <Attribute Key="copies_num" Value="670" /> <Graphics CenterX="1920.0" CenterY="2252.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="cc682" Type="Protein" GroupRef="ea96e"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876367" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="LCFA(-)" GraphId="cc8c7" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="2011.5" CenterY="1118.0" Width="71.0" Height="26.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:57560" /> </DataNode> <DataNode TextLabel="H2O" GraphId="cc9d9" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1944.0" CenterY="1115.0" Width="44.0" Height="32.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15377" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="ccf4f" Type="Protein" GroupRef="b0361"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8856140" /> <Attribute Key="copies_num" Value="2188" /> <Graphics CenterX="1780.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="Clathrin:AP-2&#xA;complex" GraphId="ccf71" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2656.0" CenterY="1227.0" Width="88.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-177505" /> </DataNode> <DataNode TextLabel="SCARB1-2 " GraphId="cd3c2" Type="Protein" GroupRef="e8b10"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-349649" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2340.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8WTV0-2" /> </DataNode> <DataNode TextLabel="ANGPTL8" GraphId="cd8ea" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="969.0" CenterY="105.0" Width="64.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q6UXH0" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="cdaa8" Type="Metabolite" GroupRef="b0361"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8856140" /> <Attribute Key="copies_num" Value="830" /> <Graphics CenterX="1780.0" CenterY="1832.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="cdae4" Type="Protein" GroupRef="cd846"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174791" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="LSR trimer" GraphId="cdcc3" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2386.0" CenterY="536.5" Width="60.0" Height="37.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8933252" /> </DataNode> <DataNode TextLabel="APOE " GraphId="cddc7" Type="Protein" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="240.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="LCFAs" GraphId="ce135" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3949.5" CenterY="982.0" Width="59.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15904" /> </DataNode> <DataNode TextLabel="HDLBP:HDL" GraphId="ce4f4" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3705.5" CenterY="1153.5" Width="65.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8858255" /> </DataNode> <DataNode TextLabel="PL" GraphId="ce5fb" Type="Metabolite"> <Attribute Key="cellular_location" Value="transport vesicle membrane" /> <Graphics CenterX="3620.0" CenterY="207.0" Width="30.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="LIPC " GraphId="ce65a" Type="Protein" GroupRef="f04a8"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-6785190" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="800.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11150" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="ce72b" Type="Metabolite" GroupRef="cd846"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174791" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="100.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="cf048" Type="Protein" GroupRef="ccab5"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-171131" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1080.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="cf6ac" Type="Metabolite" GroupRef="b6e25"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266083" /> <Attribute Key="copies_num" Value="11" /> <Graphics CenterX="1220.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="VLDLR " GraphId="cf883" Type="Protein" GroupRef="cee8c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855134" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P98155" /> </DataNode> <DataNode TextLabel="ABCG1 dimer" GraphId="cf8db" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3413.0" CenterY="698.0" Width="62.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-194222" /> </DataNode> <DataNode TextLabel="PRKACB " GraphId="cff98" Type="Protein" GroupRef="d9479"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-111920" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="2272.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P22694" /> </DataNode> <DataNode TextLabel="PRKACG " GraphId="d0032" Type="Protein" GroupRef="d9479"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-111920" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="2292.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P22612" /> </DataNode> <DataNode TextLabel="cholesterol esters" GraphId="d00e5" Type="Metabolite"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3711.0" CenterY="1600.0" Width="78.0" Height="48.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="pre-beta HDL" GraphId="d0496" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3975.5" CenterY="1534.0" Width="99.0" Height="26.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-349645" /> </DataNode> <DataNode TextLabel="FURIN " GraphId="d0a7b" Type="Protein" GroupRef="adb1d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6784618" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P09958" /> </DataNode> <DataNode TextLabel="LDL" GraphId="d1046" Type="Complex"> <Comment Source="Reactome">LDL (low density lipoproteins) are complexes of a single molecule of apoprotein B-100 (apoB-100) non-covalently associated with triacylglycerol, free cholesterol, cholesterol esters, and phospholipids. LDL complexes contain single molecules of apoB-100, but their content of lipids is variable (Chapman et al. 1988; Mateu et al. 1972; Tardieu et al. 1976). High levels of LDL in the blood are strongly correlated with increased risk of atherosclerosis, and recent studies have raised the possibility that this risk is further increased in individuals whose blood LDL population is enriched in high-density (low lipid content) LDL complexes (Rizzo and Berneis 2006). The LDL complex annotated here contains an average lipid composition.</Comment> <Attribute Key="cellular_location" Value="endosome lumen" /> <Graphics CenterX="2506.0" CenterY="1104.0" Width="30.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-171082" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="d123f" Type="Metabolite" GroupRef="a2b19"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174681" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="d174d" Type="Metabolite" GroupRef="f36a2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266308" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="1360.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="AP2A1 " GraphId="d1b24" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95782" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="d1c2a" Type="Metabolite" GroupRef="d9e63"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933291" /> <Attribute Key="copies_num" Value="682" /> <Graphics CenterX="1780.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="d20ca" Type="Metabolite" GroupRef="c4639"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="2340.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="d23b4" Type="Metabolite" GroupRef="b9478"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Attribute Key="complex_id" Value="R-HSA-8866319" /> <Attribute Key="copies_num" Value="2189" /> <Graphics CenterX="380.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="d2603" Type="Metabolite" GroupRef="ccab5"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-171131" /> <Attribute Key="copies_num" Value="670" /> <Graphics CenterX="1080.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOA2(24-100) " GraphId="d26e6" Type="Protein" GroupRef="efecd"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174769" /> <Attribute Key="copies_num" Value="361" /> <Graphics CenterX="940.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02652" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="d2840" Type="Protein" GroupRef="bb72d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349645" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="2620.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="nascent chylomicron" GraphId="d2bdc" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="1691.0" CenterY="112.5" Width="78.0" Height="39.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174626" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="d2c39" Type="Metabolite" GroupRef="d7e28"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="1220.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="PL " GraphId="d2fe8" Type="Metabolite" GroupRef="a92fc"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174792" /> <Attribute Key="copies_num" Value="61" /> <Graphics CenterX="940.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="NCEH1" GraphId="d35d7" Type="Protein"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="1981.0" CenterY="968.0" Width="66.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q6PIU2" /> </DataNode> <DataNode TextLabel="AP2A1 " GraphId="d3aac" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute 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/> <Graphics CenterX="1551.5" CenterY="1156.0" Width="47.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="d50bd" Type="Metabolite" GroupRef="b0361"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8856140" /> <Attribute Key="copies_num" Value="681" /> <Graphics CenterX="1780.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="PL " GraphId="d50ef" Type="Metabolite" GroupRef="a82b2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-176866" /> <Attribute Key="copies_num" Value="2858" /> <Graphics CenterX="1080.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="d5238" Type="Metabolite" GroupRef="f2ca5"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-174630" /> <Attribute Key="copies_num" Value="99" /> <Graphics CenterX="100.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="PL " GraphId="d54f8" Type="Metabolite" GroupRef="f7f4f"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174681" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1832.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="d55cd" Type="Metabolite" GroupRef="fe7aa"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8858255" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="2340.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="d5749" Type="Metabolite" GroupRef="dd849"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-171082" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1920.0" CenterY="2312.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="d5799" Type="Protein" GroupRef="c2ef8"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349410" /> <Attribute Key="copies_num" Value="166" /> <Graphics CenterX="1500.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="d5850" Type="Protein" GroupRef="a92fc"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174792" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="940.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="AP2A2(1-939) " GraphId="d58b0" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O94973" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="d5c90" Type="Metabolite" GroupRef="d605b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349645" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="660.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="AP2B1 " GraphId="d6232" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P63010" /> </DataNode> <DataNode TextLabel="APOA2(24-100) " GraphId="d62b9" Type="Protein" GroupRef="cd846"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174791" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="100.0" CenterY="2272.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02652" /> </DataNode> <DataNode TextLabel="chylomicron remnant" GraphId="d66b2" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1531.0" CenterY="681.0" Width="92.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174807" /> </DataNode> <DataNode TextLabel="CREB3L3(?-461)" GraphId="d679e" Type="Protein"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="413.5" CenterY="258.0" Width="61.0" Height="38.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q68CJ9" /> </DataNode> <DataNode TextLabel="PCSK9 " GraphId="d68aa" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8NBP7" /> </DataNode> <DataNode TextLabel="APOC2 gene " GraphId="d6943" Type="Protein" GroupRef="c47fc"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Attribute Key="complex_id" Value="R-HSA-6784668" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2332.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Ensembl" ID="ENSG00000234906" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="d6b9a" Type="Protein" GroupRef="dd849"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-171082" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1920.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="d6df3" Type="Metabolite" GroupRef="fc416"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266351" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="1080.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="d71de" Type="Protein" GroupRef="a2c7a"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-264851" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="AP2S1 " GraphId="d7541" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P53680" /> </DataNode> <DataNode TextLabel="CLTC " GraphId="d760c" Type="Protein" GroupRef="a8f2d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2480.0" CenterY="2432.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q00610" /> </DataNode> <DataNode TextLabel="LIPC " GraphId="d78d1" Type="Protein" GroupRef="ef513"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6785208" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="800.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11150" /> </DataNode> <DataNode TextLabel="AP2M1 " GraphId="d82cc" Type="Protein" GroupRef="c5c02"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855135" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2620.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96CW1" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="d8379" Type="Protein" GroupRef="fcf93"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174756" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="GPIHBP1:HSPG:LPL&#xA;dimer" GraphId="d846b" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="711.5" CenterY="354.0" Width="99.0" Height="40.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8857969" /> </DataNode> <DataNode TextLabel="spherical HDL:SR-BI&#xA;complex" GraphId="d8989" Type="Complex"> <BiopaxRef>df1</BiopaxRef> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3882.0" CenterY="1363.5" Width="80.0" Height="49.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-349649" /> </DataNode> <DataNode TextLabel="PCSK9" GraphId="d8d07" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2711.5" CenterY="1044.0" Width="53.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8NBP7" /> </DataNode> <DataNode TextLabel="APOA2(24-100) " GraphId="d90c7" Type="Protein" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="240.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02652" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="d928e" Type="Metabolite" GroupRef="d3c01"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="240.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="chylomicron" GraphId="d9660" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1407.5" CenterY="423.0" Width="85.0" Height="26.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174697" /> </DataNode> <DataNode TextLabel="LDLR " GraphId="d96ae" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="ATP" GraphId="d9dd4" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3143.0" CenterY="258.0" Width="40.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15422" /> </DataNode> <DataNode TextLabel="VLDLR " GraphId="d9fc4" Type="Protein" GroupRef="b415d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8854464" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1640.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P98155" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="da4eb" Type="Protein" GroupRef="e75f1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-174749" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1500.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="da54b" Type="Metabolite" GroupRef="cd76e"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-171100" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1920.0" CenterY="1832.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="da5f6" Type="Metabolite" GroupRef="cf5eb"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-174594" /> <Attribute Key="copies_num" Value="150" /> <Graphics CenterX="1640.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="cholesterol esters " GraphId="da71d" Type="Metabolite" GroupRef="e41b5"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-174658" /> <Attribute Key="copies_num" Value="153" /> <Graphics CenterX="1640.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="LDL:cholesterol&#xA;ester complex" GraphId="da826" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3087.0" CenterY="579.5" Width="118.0" Height="37.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-266339" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="da915" Type="Protein" GroupRef="fd9be"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174807" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="940.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="LIPA" GraphId="da999" Type="Protein"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Graphics CenterX="2339.0" CenterY="1153.0" Width="34.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P38571" /> </DataNode> <DataNode TextLabel="PL " GraphId="daab3" Type="Metabolite" GroupRef="db61c"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933254" /> <Attribute Key="copies_num" Value="2860" /> <Graphics CenterX="1780.0" CenterY="2292.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="dad50" Type="Metabolite" GroupRef="aa890"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266339" /> <Attribute Key="copies_num" Value="3029" /> <Graphics CenterX="1080.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="dada9" Type="Protein" GroupRef="b2a62"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-174816" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1500.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="LIPG " GraphId="db404" Type="Protein" GroupRef="b98e6"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6789313" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="2620.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9Y5X9" /> </DataNode> <DataNode TextLabel="PL " GraphId="db685" Type="Metabolite" GroupRef="b6e25"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266083" /> <Attribute Key="copies_num" Value="36" /> <Graphics CenterX="1220.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="db878" Type="Metabolite" GroupRef="e344a"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="1220.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="dc2b4" Type="Metabolite" GroupRef="c178b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855875" /> <Attribute Key="copies_num" Value="2187" /> <Graphics CenterX="520.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="AMN " GraphId="dc80e" Type="Protein" GroupRef="e20dc"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-264830" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9BXJ7" /> </DataNode> <DataNode TextLabel="LCFAs" GraphId="dc83f" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1201.5" CenterY="705.0" Width="59.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15904" /> </DataNode> <DataNode TextLabel="CETP " GraphId="dc890" Type="Protein" GroupRef="fc416"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266351" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1080.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11597" /> </DataNode> <DataNode TextLabel="PKA catalytic&#xA;subunit" GraphId="dc99a" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3223.5" CenterY="253.5" Width="81.0" Height="39.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-111920" /> </DataNode> <DataNode TextLabel="APOA5 " GraphId="dcae2" Type="Protein" GroupRef="dd6ab"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-6784718" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q6Q788" /> </DataNode> <DataNode TextLabel="APOA4 gene " GraphId="dd3eb" Type="Protein" GroupRef="c47fc"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Attribute Key="complex_id" Value="R-HSA-6784668" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2292.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Ensembl" ID="ENSG00000110244" /> </DataNode> <DataNode TextLabel="cholesterol " GraphId="dd438" Type="Metabolite" GroupRef="fa242"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-171056" /> <Attribute Key="copies_num" Value="670" /> <Graphics CenterX="1920.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHEST" GraphId="dd476" Type="Metabolite"> <Attribute Key="cellular_location" Value="lipid droplet" /> <Graphics CenterX="1880.5" CenterY="1062.0" Width="55.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="dd9ef" Type="Metabolite" GroupRef="e75f1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-174749" /> <Attribute Key="copies_num" Value="150" /> <Graphics CenterX="1500.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="PCSK6 " GraphId="ddc3f" Type="Protein" GroupRef="adb1d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6784618" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P29122" /> </DataNode> <DataNode TextLabel="pre-VLDL" GraphId="ddda8" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="2186.5" CenterY="65.0" Width="65.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6784871" /> </DataNode> <DataNode TextLabel="GPIHBP1" GraphId="de1dd" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="711.5" CenterY="275.0" Width="65.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8IV16" /> </DataNode> <DataNode TextLabel="cholesterol esters " GraphId="de5df" Type="Metabolite" GroupRef="e8b10"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-349649" /> <Attribute Key="copies_num" Value="202" /> <Graphics CenterX="2340.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="MTP:PDI:lipid&#xA;complex" GraphId="de690" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="2108.0" CenterY="235.0" Width="90.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174681" /> </DataNode> <DataNode TextLabel="AP2S1 " GraphId="de7aa" Type="Protein" GroupRef="e010b"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-2130671" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P53680" /> </DataNode> <DataNode TextLabel="chylomicron&#xA;remnant:apoE&#xA;complex" GraphId="de7c9" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1725.5" CenterY="681.5" Width="93.0" Height="51.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174792" /> </DataNode> <DataNode TextLabel="VLDL:PCSK9" GraphId="de927" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3251.5" CenterY="1195.0" Width="65.0" Height="32.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8855118" /> </DataNode> <DataNode TextLabel="ALB" GraphId="def39" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3996.5" CenterY="730.5" Width="45.0" Height="25.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02768" /> </DataNode> <DataNode TextLabel="VLDLR " GraphId="df148" Type="Protein" GroupRef="dd10f"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855118" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P98155" /> </DataNode> <DataNode TextLabel="AP2M1 " GraphId="df206" Type="Protein" GroupRef="a8f2d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2332.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96CW1" /> </DataNode> <DataNode TextLabel="PL " GraphId="df602" Type="Metabolite" GroupRef="a2b19"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174681" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="spherical&#xA;HDL:apoC-II:apoC-III:apoE" GraphId="df7d5" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1691.0" CenterY="463.0" Width="96.0" Height="52.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174643" /> </DataNode> <DataNode TextLabel="PL" GraphId="df877" Type="Metabolite"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="2044.0" CenterY="65.0" Width="30.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="enlarged spherical&#xA;HDL" GraphId="dfce2" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3640.0" CenterY="879.5" Width="74.0" Height="47.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8855688" /> </DataNode> <DataNode TextLabel="LDLR " GraphId="dfd4e" Type="Protein" GroupRef="e41b5"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-174658" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1640.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="LDL:LDLR complex" GraphId="dff99" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2658.0" CenterY="822.0" Width="70.0" Height="40.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-171100" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="e0365" Type="Metabolite" GroupRef="e3b46"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855688" /> <Attribute Key="copies_num" Value="345" /> <Graphics CenterX="1360.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOC4 " GraphId="e0602" Type="Protein" GroupRef="b0361"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8856140" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1780.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P55056" /> </DataNode> <DataNode TextLabel="APOA4" GraphId="e06cc" Type="Protein"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="1479.0" CenterY="235.0" Width="50.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06727" /> </DataNode> <DataNode TextLabel="CLTC " GraphId="e07c2" Type="Protein" GroupRef="aa20d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2060.0" CenterY="2392.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q00610" /> </DataNode> <DataNode TextLabel="LDLRAP1" GraphId="e0d68" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="1599.0" CenterY="1004.0" Width="74.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q5SW96" /> </DataNode> <DataNode TextLabel="BMP1-3 " GraphId="e1027" Type="Protein" GroupRef="b7e67"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-264759" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P13497-3" /> </DataNode> <DataNode TextLabel="acyl-CoA" GraphId="e10a6" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="2090.0" CenterY="828.0" Width="68.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17984" /> </DataNode> <DataNode TextLabel="PCSK9 " GraphId="e11b4" Type="Protein" GroupRef="e6276"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6784730" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8NBP7" /> </DataNode> <DataNode TextLabel="PL " GraphId="e1325" Type="Metabolite" GroupRef="b9478"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Attribute Key="complex_id" Value="R-HSA-8866319" /> <Attribute Key="copies_num" Value="461" /> <Graphics CenterX="380.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="e1471" Type="Metabolite"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3514.5" CenterY="627.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="e157c" Type="Metabolite" GroupRef="e3b46"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855688" /> <Attribute Key="copies_num" Value="45" /> <Graphics CenterX="1360.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="ANGPTL3" GraphId="e172b" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="888.0" CenterY="105.0" Width="64.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9Y5C1" /> </DataNode> <DataNode TextLabel="AP2M1 " GraphId="e181d" Type="Protein" GroupRef="cee8c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855134" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96CW1" /> </DataNode> <DataNode TextLabel="PL " GraphId="e1c10" Type="Metabolite" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="60" /> <Graphics CenterX="800.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="chylomicron&#xA;remnant:apoE:LDLR&#xA;complex" GraphId="e1d2c" Type="Complex"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Graphics CenterX="1479.5" CenterY="1064.0" Width="129.0" Height="52.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174658" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="e1f7f" Type="Protein" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="149" /> <Graphics CenterX="800.0" CenterY="2272.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="AP2S1 " GraphId="e2170" Type="Protein" GroupRef="c5c02"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855135" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2620.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P53680" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="e2369" Type="Protein" GroupRef="a601d"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876365" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="1832.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="LIPC " GraphId="e2f6a" Type="Protein" GroupRef="c2e2b"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-6785173" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="800.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11150" /> </DataNode> <DataNode TextLabel="VLDL:PCSK9:Clathrin:AP2" GraphId="e302a" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3051.5" CenterY="1163.0" Width="79.0" Height="48.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8855134" /> </DataNode> <DataNode TextLabel="APOA4 " GraphId="e31c7" Type="Protein" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="240.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06727" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="e3864" Type="Metabolite" GroupRef="c178b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855875" /> <Attribute Key="copies_num" Value="829" /> <Graphics CenterX="520.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="e3a85" Type="Metabolite" GroupRef="e344a"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="1220.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="e3af0" Type="Metabolite" GroupRef="e75f1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-174749" /> <Attribute Key="copies_num" Value="151" /> <Graphics CenterX="1500.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="LPL dimer" GraphId="e3cd3" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="797.5" CenterY="104.5" Width="53.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174592" /> </DataNode> <DataNode TextLabel="LDL:LDLR complex" GraphId="e41ec" Type="Complex"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Graphics CenterX="2588.5" CenterY="903.0" Width="73.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-171108" /> </DataNode> <DataNode TextLabel="PL " GraphId="e4328" Type="Metabolite" GroupRef="b9853"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266340" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="1080.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="TAGs" GraphId="e4361" Type="Metabolite"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="2101.0" CenterY="65.0" Width="48.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="phosphatidylcholines" GraphId="e4364" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3813.0" CenterY="537.0" Width="144.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16110" /> </DataNode> <DataNode TextLabel="LMF2 " GraphId="e4761" Type="Protein" GroupRef="c2e2b"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-6785173" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="800.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9BU23" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="e4824" Type="Protein" GroupRef="cd846"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174791" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="100.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="VLDLR " GraphId="e4a51" Type="Protein" GroupRef="c5c02"> <Attribute Key="cellular_location" Value="lysosomal membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855135" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2620.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P98155" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="e4f3b" Type="Metabolite" GroupRef="e9db1"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="2340.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOE" GraphId="e5792" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1566.5" CenterY="736.0" Width="45.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="AP2A2(1-939) " GraphId="e5b73" Type="Protein" GroupRef="e010b"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-2130671" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O94973" /> </DataNode> <DataNode TextLabel="AP2A1 " GraphId="e5de8" Type="Protein" GroupRef="c5c02"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855135" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2620.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95782" /> </DataNode> <DataNode TextLabel="AP2M1 " GraphId="e616f" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96CW1" /> </DataNode> <DataNode TextLabel="LDLR " GraphId="e61bb" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2200.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="APOC2 " GraphId="e63cc" Type="Protein" GroupRef="d7e28"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="1220.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02655" /> </DataNode> <DataNode TextLabel="LDL" GraphId="e64c0" Type="Complex"> <Comment Source="Reactome">LDL (low density lipoproteins) are complexes of a single molecule of apoprotein B-100 (apoB-100) non-covalently associated with triacylglycerol, free cholesterol, cholesterol esters, and phospholipids. LDL complexes contain single molecules of apoB-100, but their content of lipids is variable (Chapman et al. 1988; Mateu et al. 1972; Tardieu et al. 1976). High levels of LDL in the blood are strongly correlated with increased risk of atherosclerosis, and recent studies have raised the possibility that this risk is further increased in individuals whose blood LDL population is enriched in high-density (low lipid content) LDL complexes (Rizzo and Berneis 2006). The LDL complex annotated here contains an average lipid composition.</Comment> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2786.0" CenterY="621.5" Width="46.0" Height="19.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-171131" /> </DataNode> <DataNode TextLabel="NPC2:CHOL" GraphId="e6653" Type="Complex"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Graphics CenterX="2332.0" CenterY="888.5" Width="62.0" Height="35.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8876460" /> </DataNode> <DataNode TextLabel="Pi" GraphId="e6a79" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3688.5" CenterY="252.0" Width="27.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:18367" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="e6aa3" Type="Protein" GroupRef="f801c"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-171108" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1920.0" CenterY="1912.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="e6aa4" Type="Protein" GroupRef="c0ffc"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174626" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="APOE " GraphId="e6ad4" Type="Protein" GroupRef="e41b5"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-174658" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1640.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="APOA4 " GraphId="e72ed" Type="Protein" GroupRef="c0ffc"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174626" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="100.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06727" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="e7686" Type="Metabolite" GroupRef="d4013"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-216752" /> <Attribute Key="copies_num" Value="11" /> <Graphics CenterX="520.0" CenterY="2452.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="e76d4" Type="Metabolite"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Graphics CenterX="2419.5" CenterY="201.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="e7764" Type="Protein" GroupRef="fe7aa"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8858255" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="2340.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="DAGs" GraphId="e77c6" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3979.5" CenterY="938.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:18035" /> </DataNode> <DataNode TextLabel="PL " GraphId="e7db8" Type="Metabolite" GroupRef="f36a2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266308" /> <Attribute Key="copies_num" Value="182" /> <Graphics CenterX="1360.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="ATP" GraphId="e7df7" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="3515.0" CenterY="242.0" Width="40.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15422" /> </DataNode> <DataNode TextLabel="A2M tetramer" GraphId="e7e2b" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3249.0" CenterY="370.0" Width="90.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-158255" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="e80f0" Type="Metabolite" GroupRef="ad7ae"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266348" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="1360.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="LCAT" GraphId="e8113" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3806.0" CenterY="613.0" Width="56.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04180" /> </DataNode> <DataNode TextLabel="VLDL (-APOC1,C4)" GraphId="e82ca" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2526.0" CenterY="436.0" Width="98.0" Height="40.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8866325" /> </DataNode> <DataNode TextLabel="PCSK9:LDLR" GraphId="e87ea" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2656.0" CenterY="1172.5" Width="58.0" Height="37.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6784730" /> </DataNode> <DataNode TextLabel="4xPALM-C-ABCA1 " GraphId="e888f" Type="Protein" GroupRef="ed01e"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-5682073" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="520.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95477" /> </DataNode> <DataNode TextLabel="CIDEC " GraphId="e8e50" Type="Protein" GroupRef="dd6ab"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-6784718" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96AQ7-1" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="e8f0f" Type="Protein" GroupRef="d3c01"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="240.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="e927f" Type="Metabolite" GroupRef="db61c"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933254" /> <Attribute Key="copies_num" Value="3029" /> <Graphics CenterX="1780.0" CenterY="2312.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="e96af" Type="Metabolite" GroupRef="c4639"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="43" /> <Graphics CenterX="2340.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="discoidal HDL" GraphId="e97ed" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3641.0" CenterY="487.0" Width="90.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-216752" /> </DataNode> <DataNode TextLabel="CUBN:AMN" GraphId="e9928" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3624.5" CenterY="1213.0" Width="71.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-264830" /> </DataNode> <DataNode TextLabel="nascent chylomicron" GraphId="e9d49" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1690.5" CenterY="393.0" Width="85.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174791" /> </DataNode> <DataNode TextLabel="albumin:2-lysophosphatidylcholine complex" GraphId="e9fad" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3944.5" CenterY="842.0" Width="105.0" Height="52.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-264677" /> </DataNode> <DataNode TextLabel="TAGs" GraphId="ea166" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="664.0" CenterY="698.0" Width="48.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="LPL " GraphId="ea748" Type="Protein" GroupRef="af498"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8857969" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="660.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06858" /> </DataNode> <DataNode TextLabel="LPL " GraphId="ea829" Type="Protein" GroupRef="f1fa1"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8867477" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="660.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06858" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="ea928" Type="Protein" GroupRef="cd76e"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-171100" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1920.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="LDLR " GraphId="eab9b" Type="Protein" GroupRef="e75f1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-174749" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1500.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="LPL " GraphId="eb113" Type="Protein" GroupRef="d9c35"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174592" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="660.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06858" /> </DataNode> <DataNode TextLabel="AP2M1 " GraphId="eb122" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1972.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96CW1" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="eb21e" Type="Metabolite" GroupRef="b888d"> <Attribute Key="cellular_location" Value="lysosomal membrane" /> <Attribute Key="complex_id" Value="R-HSA-8876475" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="eb330" Type="Metabolite" GroupRef="e344a"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="43" /> <Graphics CenterX="1220.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="eb791" Type="Metabolite" GroupRef="f801c"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-171108" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1920.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="NPC1 " GraphId="ebc17" Type="Protein" GroupRef="b888d"> <Attribute Key="cellular_location" Value="lysosomal membrane" /> <Attribute Key="complex_id" Value="R-HSA-8876475" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O15118" /> </DataNode> <DataNode TextLabel="CES3" GraphId="ebdeb" Type="Protein"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1974.5" CenterY="1200.0" Width="49.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q6UWW8" /> </DataNode> <DataNode TextLabel="AP2A2(1-939) " GraphId="ebe0b" Type="Protein" GroupRef="aa20d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2352.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O94973" /> </DataNode> <DataNode TextLabel="P4HB " GraphId="ebe64" Type="Protein" GroupRef="f7f4f"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174681" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P07237" /> </DataNode> <DataNode TextLabel="PL " GraphId="ebfa5" Type="Metabolite" GroupRef="fcf93"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174756" /> <Attribute Key="copies_num" Value="60" /> <Graphics CenterX="100.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOC4" GraphId="ec228" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2427.5" CenterY="390.0" Width="49.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P55056" /> </DataNode> <DataNode TextLabel="APOBR " GraphId="ec599" Type="Protein" GroupRef="befb8"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8854406" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1780.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q0VD83" /> </DataNode> <DataNode TextLabel="cholesterol esters " GraphId="eca60" Type="Metabolite" GroupRef="fa242"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-171056" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1920.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOF" GraphId="ece25" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2957.5" CenterY="560.5" Width="57.0" Height="23.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q13790" /> </DataNode> <DataNode TextLabel="CETP:cholesterol&#xA;ester complex" GraphId="ecee7" Type="Complex"> <BiopaxRef>cc5</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2909.0" CenterY="667.5" Width="118.0" Height="39.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-266340" /> </DataNode> <DataNode TextLabel="APOA4,APOA5,APOC2,CIDEC,FGF21 genes" GraphId="ed487" Type="Complex"> <Attribute Key="cellular_location" Value="nucleoplasm" /> <Graphics CenterX="154.5" CenterY="133.5" Width="135.0" Height="49.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6784668" /> </DataNode> <DataNode TextLabel="SOAT1,2" GraphId="ed5c7" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="1985.0" CenterY="880.5" Width="72.0" Height="23.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8876694" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="ed60e" Type="Metabolite" GroupRef="c0ffc"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174626" /> <Attribute Key="copies_num" Value="202" /> <Graphics CenterX="100.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="PL " GraphId="ed911" Type="Metabolite" GroupRef="d9e63"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933291" /> <Attribute Key="copies_num" Value="1290" /> <Graphics CenterX="1780.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="ANGPTL3:ANGPTL8" GraphId="edf5d" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="930.5" CenterY="227.5" Width="85.0" Height="35.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6784846" /> </DataNode> <DataNode TextLabel="Zn2+ " GraphId="ee091" Type="Metabolite" GroupRef="b7e67"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-264759" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:29105" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="ee62f" Type="Protein" GroupRef="dd4ec"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174697" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="240.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="LCAT " GraphId="ee759" Type="Protein" GroupRef="f36a2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266308" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="1360.0" CenterY="1992.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04180" /> </DataNode> <DataNode TextLabel="VLDL" GraphId="ee959" Type="Complex"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Graphics CenterX="2526.5" CenterY="109.0" Width="47.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8866319" /> </DataNode> <DataNode TextLabel="PL " GraphId="eebbf" Type="Metabolite" GroupRef="cf5eb"> <Attribute Key="cellular_location" Value="endosome lumen" /> <Attribute Key="complex_id" Value="R-HSA-174594" /> <Attribute Key="copies_num" Value="61" /> <Graphics CenterX="1640.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="HDLBP " GraphId="eecaa" Type="Protein" GroupRef="fe7aa"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8858255" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2340.0" CenterY="1692.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q00341" /> </DataNode> <DataNode TextLabel="APOC2 " GraphId="eee30" Type="Protein" GroupRef="d3c01"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="240.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02655" /> </DataNode> <DataNode TextLabel="LIPC dimer" GraphId="ef242" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="773.0" CenterY="499.0" Width="54.0" Height="34.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6785179" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="ef59e" Type="Metabolite" GroupRef="d3c01"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="43" /> <Graphics CenterX="240.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="ef5fa" Type="Metabolite" GroupRef="d7e28"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="1220.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="1-acyl LPC" GraphId="ef62a" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3943.0" CenterY="671.0" Width="60.0" Height="42.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17504" /> </DataNode> <DataNode TextLabel="APOB(28-2179)" GraphId="ef746" Type="Protein"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="1200.5" CenterY="162.5" Width="81.0" Height="31.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="TG-depleted&#xA;chylomicron" GraphId="ef8cb" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1297.5" CenterY="639.5" Width="103.0" Height="35.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174798" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="eff3c" Type="Metabolite" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="152" /> <Graphics CenterX="800.0" CenterY="2412.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="f00fd" Type="Protein" GroupRef="b1640"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-264684" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1220.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="f036a" Type="Metabolite" GroupRef="b0361"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8856140" /> <Attribute Key="copies_num" Value="2188" /> <Graphics CenterX="1780.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="f05e4" Type="Protein" GroupRef="f2ca5"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-174630" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="1652.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="AP2B1 " GraphId="f0942" Type="Protein" GroupRef="aa20d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2272.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P63010" /> </DataNode> <DataNode TextLabel="LDLR " GraphId="f09de" Type="Protein" GroupRef="f801c"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-171108" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1920.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P01130" /> </DataNode> <DataNode TextLabel="LPA" GraphId="f0c63" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2686.0" CenterY="573.0" Width="46.0" Height="26.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P08519" /> </DataNode> <DataNode TextLabel="AP2S1 " GraphId="f0cc0" Type="Protein" GroupRef="aa20d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2312.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P53680" /> </DataNode> <DataNode TextLabel="PL " GraphId="f0eba" Type="Metabolite" GroupRef="d4013"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-216752" /> <Attribute Key="copies_num" Value="35" /> <Graphics CenterX="520.0" CenterY="2472.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOA5" GraphId="f11cd" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1177.0" CenterY="523.5" Width="54.0" Height="23.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q6Q788" /> </DataNode> <DataNode TextLabel="APOB(28-2179) " GraphId="f15b9" Type="Protein" GroupRef="e41b5"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-174658" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1640.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="PL " GraphId="f163f" Type="Metabolite" GroupRef="b2a62"> <Attribute Key="cellular_location" Value="clathrin-coated endocytic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-174816" /> <Attribute Key="copies_num" Value="61" /> <Graphics CenterX="1500.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOA1(25-267) " GraphId="f16b2" Type="Protein" GroupRef="c0ffc"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174626" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="100.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="APOE " GraphId="f1843" Type="Protein" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="149" /> <Graphics CenterX="800.0" CenterY="2372.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02649" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="f19f4" Type="Metabolite" GroupRef="c0ffc"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174626" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="100.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="4xPALM-C-ABCA1&#xA;tetramer" GraphId="f1a2e" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3082.5" CenterY="319.0" Width="123.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-5682073" /> </DataNode> <DataNode TextLabel="Lp(a)" GraphId="f2354" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="2687.5" CenterY="681.0" Width="51.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-176866" /> </DataNode> <DataNode TextLabel="CLTC " GraphId="f2419" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="2200.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q00610" /> </DataNode> <DataNode TextLabel="cholesterol esters " GraphId="f2608" Type="Metabolite" GroupRef="cd76e"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-171100" /> <Attribute Key="copies_num" Value="2169" /> <Graphics CenterX="1920.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="PLTP" GraphId="f2656" Type="Complex"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3660.0" CenterY="786.5" Width="52.0" Height="29.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-194227" /> </DataNode> <DataNode TextLabel="DAGs" GraphId="f286b" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="886.5" CenterY="698.0" Width="49.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:18035" /> </DataNode> <DataNode TextLabel="HSPG " GraphId="f2e71" Type="Metabolite" GroupRef="f1fa1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8867477" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:24499" /> </DataNode> <DataNode TextLabel="AP2S1 " GraphId="f31fb" Type="Protein" GroupRef="cee8c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855134" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P53680" /> </DataNode> <DataNode TextLabel="PL " GraphId="f335c" Type="Metabolite" GroupRef="e8b10"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-349649" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="2340.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="f3732" Type="Protein" GroupRef="b415d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8854464" /> <Attribute Key="copies_num" Value="2187" /> <Graphics CenterX="1640.0" CenterY="2172.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="PL " GraphId="f3906" Type="Metabolite" GroupRef="c815b"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784871" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="f397b" Type="Metabolite" GroupRef="f36a2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266308" /> <Attribute Key="copies_num" Value="43" /> <Graphics CenterX="1360.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="f39f5" Type="Metabolite" GroupRef="b415d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8854464" /> <Attribute Key="copies_num" Value="680" /> <Graphics CenterX="1640.0" CenterY="2092.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="pre-VLDL" GraphId="f3b98" Type="Complex"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Graphics CenterX="2350.0" CenterY="109.0" Width="68.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-8866311" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="f3d04" Type="Metabolite" GroupRef="cd846"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174791" /> <Attribute Key="copies_num" Value="200" /> <Graphics CenterX="100.0" CenterY="2292.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="f430d" Type="Metabolite" GroupRef="bb72d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349645" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="2620.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHEST" GraphId="f4356" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3881.5" CenterY="719.5" Width="53.0" Height="35.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="CoA-SH" GraphId="f4548" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1886.0" CenterY="829.0" Width="64.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15346" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="f45ac" Type="Metabolite" GroupRef="e3b46"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855688" /> <Attribute Key="copies_num" Value="364" /> <Graphics CenterX="1360.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="PL " GraphId="f494d" Type="Metabolite" GroupRef="c4639"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="182" /> <Graphics CenterX="2340.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="PL " GraphId="f4a1d" Type="Metabolite" GroupRef="fd9be"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174807" /> <Attribute Key="copies_num" Value="60" /> <Graphics CenterX="940.0" CenterY="1712.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="MTTP " GraphId="f4c2f" Type="Protein" GroupRef="f7f4f"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174681" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1792.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P55157" /> </DataNode> <DataNode TextLabel="CHEST" GraphId="f4c77" Type="Metabolite"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Graphics CenterX="2477.5" CenterY="198.0" Width="55.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="f4c88" Type="Protein" GroupRef="e9db1"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-265523" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="2340.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="ANGPTL3 " GraphId="f4cd5" Type="Protein" GroupRef="bdd41"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6784846" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="2052.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9Y5C1" /> </DataNode> <DataNode TextLabel="CLTA " GraphId="f4f15" Type="Protein" GroupRef="ac60f"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784728" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2200.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P09496" /> </DataNode> <DataNode TextLabel="AP2S1 " GraphId="f501a" Type="Protein" GroupRef="c6b32"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-6784733" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2200.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P53680" /> </DataNode> <DataNode TextLabel="PL" GraphId="f5021" Type="Metabolite"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3778.0" CenterY="319.0" Width="30.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHOL" GraphId="f50e2" Type="Metabolite"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Graphics CenterX="2308.5" CenterY="1033.0" Width="51.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="PL " GraphId="f530e" Type="Metabolite" GroupRef="c178b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855875" /> <Attribute Key="copies_num" Value="1288" /> <Graphics CenterX="520.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="PL " GraphId="f535b" Type="Metabolite" GroupRef="cd846"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174791" /> <Attribute Key="copies_num" Value="60" /> <Graphics CenterX="100.0" CenterY="2192.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="f54b3" Type="Metabolite" GroupRef="efecd"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174769" /> <Attribute Key="copies_num" Value="44" /> <Graphics CenterX="940.0" CenterY="1892.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="PCSK9 " GraphId="f586c" Type="Protein" GroupRef="dd10f"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855118" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2032.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q8NBP7" /> </DataNode> <DataNode TextLabel="PL " GraphId="f58fd" Type="Metabolite" GroupRef="e41b5"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-174658" /> <Attribute Key="copies_num" Value="150" /> <Graphics CenterX="1640.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOA4,APOA5,APOC2,CIDEC,FGF21" GraphId="f599c" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="155.5" CenterY="321.0" Width="129.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6784718" /> </DataNode> <DataNode TextLabel="PCSK9:LDLR:Clathrin:AP2" GraphId="f5aa0" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="2664.5" CenterY="1287.5" Width="97.0" Height="37.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-6784733" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="f5b4a" Type="Metabolite" GroupRef="be863"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876460" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="APOC3 " GraphId="f5bae" Type="Protein" GroupRef="d7e28"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="360" /> <Graphics CenterX="1220.0" CenterY="2232.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02656" /> </DataNode> <DataNode TextLabel="LCAT" GraphId="f5bb9" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3490.0" CenterY="839.0" Width="56.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04180" /> </DataNode> <DataNode TextLabel="AP2B1 " GraphId="f5dc3" Type="Protein" GroupRef="cee8c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855134" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2480.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P63010" /> </DataNode> <DataNode TextLabel="PL " GraphId="f6102" Type="Metabolite" GroupRef="a61cf"> <Attribute Key="cellular_location" Value="smooth endoplasmic reticulum" /> <Attribute Key="complex_id" Value="R-HSA-8866311" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="ALB " GraphId="f6145" Type="Protein" GroupRef="c5632"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-264677" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1360.0" CenterY="1932.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02768" /> </DataNode> <DataNode TextLabel="APOA2(24-100)" GraphId="f658c" Type="Protein"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="1432.0" CenterY="155.5" Width="70.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02652" /> </DataNode> <DataNode TextLabel="CLTA " GraphId="f669e" Type="Protein" GroupRef="e010b"> <Attribute Key="cellular_location" Value="endolysosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-2130671" /> <Attribute Key="copies_num" Value="5" /> <Graphics 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Type="Metabolite" GroupRef="fe7aa"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8858255" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="2340.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="APOC3" GraphId="f78f2" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1156.0" CenterY="606.5" Width="56.0" Height="21.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02656" /> </DataNode> <DataNode TextLabel="PL " GraphId="f7e62" Type="Metabolite" GroupRef="a601d"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Attribute Key="complex_id" Value="R-HSA-8876365" /> <Attribute Key="copies_num" Value="1359" /> <Graphics CenterX="2060.0" CenterY="1872.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="f7f87" Type="Metabolite" GroupRef="c2ef8"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-349410" /> <Attribute Key="copies_num" Value="205" /> <Graphics CenterX="1500.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="LPA " GraphId="f8727" Type="Protein" GroupRef="a82b2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-176866" /> <Attribute Key="copies_num" Value="3027" /> <Graphics CenterX="1080.0" CenterY="2272.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P08519" /> </DataNode> <DataNode TextLabel="SOAT1 " GraphId="f87dc" Type="Protein" GroupRef="c76ec"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Attribute Key="complex_id" Value="R-HSA-8876694" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P35610" /> </DataNode> <DataNode TextLabel="CREB3L3(1-?)" GraphId="f8b89" Type="Protein"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="354.0" CenterY="211.5" Width="60.0" Height="33.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q68CJ9" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="f8cc3" Type="Protein" GroupRef="f36a2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266308" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="1360.0" CenterY="2012.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="CETP:triacylglycerol&#xA;complex" GraphId="f939f" Type="Complex"> <BiopaxRef>cc5</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3089.0" CenterY="655.0" Width="94.0" Height="46.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-266351" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="f9590" Type="Metabolite" GroupRef="f7f4f"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Attribute Key="complex_id" Value="R-HSA-174681" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1852.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="LIPC " GraphId="f95bd" Type="Protein" GroupRef="a6e4f"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-6785179" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="800.0" CenterY="2072.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11150" /> </DataNode> <DataNode TextLabel="SAR1B" GraphId="f9a3b" Type="Protein"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1749.5" CenterY="195.0" Width="45.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9Y6B6" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="f9a8c" Type="Metabolite" GroupRef="a82b2"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-176866" /> <Attribute Key="copies_num" Value="2169" /> <Graphics CenterX="1080.0" CenterY="2212.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="ApoB-48:TG:PL&#xA;complex" GraphId="f9f3d" Type="Complex"> <Attribute Key="cellular_location" Value="endoplasmic reticulum lumen" /> <Graphics CenterX="1439.5" CenterY="109.0" Width="103.0" Height="38.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174756" /> </DataNode> <DataNode TextLabel="CLTC " GraphId="fa03f" Type="Protein" GroupRef="cee8c"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-8855134" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="2480.0" CenterY="2252.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q00610" /> </DataNode> <DataNode TextLabel="APOA4 " GraphId="fa47a" Type="Protein" GroupRef="cd846"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174791" /> <Attribute Key="copies_num" Value="199" /> <Graphics CenterX="100.0" CenterY="2252.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P06727" /> </DataNode> <DataNode TextLabel="spherical&#xA;HDL:apoA-I:apoA-II:apoA-IV:apoC-II:apoC-III" GraphId="fa531" Type="Complex"> <BiopaxRef>f95</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="1570.5" CenterY="610.5" Width="111.0" Height="63.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-174769" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="fa59c" Type="Protein" GroupRef="ad7ae"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266348" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="1360.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="CHOL " GraphId="fabfe" Type="Metabolite" GroupRef="fe7aa"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8858255" /> <Attribute Key="copies_num" Value="43" /> <Graphics CenterX="2340.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16113" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="fac9d" Type="Metabolite" GroupRef="ccab5"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-171131" /> <Attribute Key="copies_num" Value="2169" /> <Graphics CenterX="1080.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="TAGs " GraphId="fb063" Type="Metabolite" GroupRef="b6aab"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174798" /> <Attribute Key="copies_num" Value="149" /> <Graphics CenterX="800.0" CenterY="2252.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17855" /> </DataNode> <DataNode TextLabel="PL " GraphId="fb16c" Type="Metabolite" GroupRef="fc416"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-266351" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1080.0" CenterY="1952.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="fb383" Type="Protein" GroupRef="d9e63"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933291" /> <Attribute Key="copies_num" Value="2189" /> <Graphics CenterX="1780.0" CenterY="2152.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="APOA1(25-266) " GraphId="fb621" Type="Protein" GroupRef="c32b3"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-5682094" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="2352.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="APOC2 " GraphId="fb6e3" Type="Protein" GroupRef="dd6ab"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-6784718" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02655" /> </DataNode> <DataNode TextLabel="FA" GraphId="fb7c6" Type="Metabolite"> <Attribute Key="cellular_location" Value="lysosomal lumen" /> <Graphics CenterX="2234.0" CenterY="1050.0" Width="32.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:35366" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="fb82b" Type="Metabolite" GroupRef="d3c01"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-174643" /> <Attribute Key="copies_num" Value="341" /> <Graphics CenterX="240.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="PL " GraphId="fbde4" Type="Metabolite" GroupRef="fa242"> <Attribute Key="cellular_location" Value="endosome membrane" /> <Attribute Key="complex_id" Value="R-HSA-171056" /> <Attribute Key="copies_num" Value="1359" /> <Graphics CenterX="1920.0" CenterY="2112.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="APOC1 " GraphId="fbe33" Type="Protein" GroupRef="b0361"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8856140" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="1780.0" CenterY="1772.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02654" /> </DataNode> <DataNode TextLabel="PL " GraphId="fc04e" Type="Metabolite" GroupRef="ccab5"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-171131" /> <Attribute Key="copies_num" Value="2858" /> <Graphics CenterX="1080.0" CenterY="1752.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="4xPALM-C-p-2S-ABCA1 " GraphId="fc064" Type="Protein" GroupRef="c32b3"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-5682094" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="520.0" CenterY="2372.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95477" /> </DataNode> <DataNode TextLabel="PL" GraphId="fc14b" Type="Metabolite"> <Attribute Key="cellular_location" Value="endoplasmic reticulum membrane" /> <Graphics CenterX="1253.0" CenterY="58.0" Width="30.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="CHEST " GraphId="fc1c1" Type="Metabolite" GroupRef="db61c"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8933254" /> <Attribute Key="copies_num" Value="2171" /> <Graphics CenterX="1780.0" CenterY="2272.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17002" /> </DataNode> <DataNode TextLabel="PL " GraphId="fc372" Type="Metabolite" GroupRef="e3b46"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855688" /> <Attribute Key="copies_num" Value="186" /> <Graphics CenterX="1360.0" CenterY="1732.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="FAs" GraphId="fc3d3" Type="Metabolite"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="846.5" CenterY="735.0" Width="37.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:35366" /> </DataNode> <DataNode TextLabel="AP2A1 " GraphId="fc487" Type="Protein" GroupRef="aa20d"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-177505" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="2060.0" CenterY="2332.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O95782" /> </DataNode> <DataNode TextLabel="PL " GraphId="fc664" Type="Metabolite" GroupRef="b415d"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8854464" /> <Attribute Key="copies_num" Value="1288" /> <Graphics CenterX="1640.0" CenterY="2132.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16247" /> </DataNode> <DataNode TextLabel="Ub-K839-VLDLR" GraphId="fc84a" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="3254.5" CenterY="1421.5" Width="75.0" Height="43.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P98155" /> </DataNode> <DataNode TextLabel="APOA1(25-266)" GraphId="fc97b" Type="Protein"> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3553.0" CenterY="1251.0" Width="66.0" Height="42.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P02647" /> </DataNode> <DataNode TextLabel="APOB(28-4563) " GraphId="fc995" Type="Protein" GroupRef="c178b"> <Attribute Key="cellular_location" Value="extracellular region" /> <Attribute Key="complex_id" Value="R-HSA-8855875" /> <Attribute Key="copies_num" Value="2187" /> <Graphics CenterX="520.0" CenterY="1812.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P04114" /> </DataNode> <DataNode TextLabel="CETP:spherical&#xA;HDL:torcetrapib&#xA;complex" GraphId="fca06" Type="Complex"> <BiopaxRef>b30</BiopaxRef> <Attribute Key="cellular_location" Value="extracellular region" /> <Graphics CenterX="3089.5" CenterY="905.5" Width="115.0" Height="57.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-349410" 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APOBR dimer binds to APO-B48 in TRLs or the APO-B48 equivalent domain of APO-B100 in HTG-VLDLs (Bradley et al. 1999). Macrophages can play multifunctional roles in the pathogenesis and progression of atherosclerosis, in which they are important for intracellular lipid accumulation and foam cell formation. Lipid-filled foam cells are seen in atherosclerotic lesions (Brown et al. 2000, Takahashi et al. 2002). PPAR alpha and gamma activators and the blood cholesterol-lowering statin pitavastatin suppress the APOBR pathway in vivo, diminishing APOBR-mediated macrophage lipid accumulation and suggesting an antiatherogenic effect for these suppressors (Haraguchi et al. 2003, Kawakami et al. 2005).</Comment> <BiopaxRef>cba</BiopaxRef> <BiopaxRef>e4b</BiopaxRef> <BiopaxRef>dee</BiopaxRef> <BiopaxRef>d36</BiopaxRef> <BiopaxRef>f17</BiopaxRef> <BiopaxRef>b6d</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2168.0" Y="537.0" /> <Point X="2231.0" Y="537.0" /> <Anchor Position="0.0" Shape="None" GraphId="b77ee" /> <Anchor Position="0.99" Shape="None" GraphId="e9947" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8854408" /> </Interaction> <Interaction GraphId="a16f1"> <Comment Source="Reactome">Spherical HDL particles can bind apoC-II, apoC-III and and apoE proteins. 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Heparan sulfate proteoglycan (HSPG) serves as an membrane anchor for LPL dimer but for LPL to reach its site of action in capillaries, it binds to glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), an endothelial cell membrane-bound protein. Once bound, GPIHBP1 transports LPL from within interstitial spaces, across endothelial cells to the capillary lumen (Gin et al. 2007, Young et al. 2011, Adeyo et al. 2012). Defects in GPIHBP1 can cause mislocalisation of LPL leading to severe hypertriglyceridaemia and hyperlipoproteinemia type ID (MIM:615947) (Adeyo et al. 2012, Wang &amp; Hegele 2007, Beigneux et al. 2009, Beigneux et al. 2015).</Comment> <BiopaxRef>eff</BiopaxRef> <BiopaxRef>a13</BiopaxRef> <BiopaxRef>ca1</BiopaxRef> <BiopaxRef>d85</BiopaxRef> <BiopaxRef>d9b</BiopaxRef> <BiopaxRef>f26</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="773.0" Y="250.0" /> <Point X="730.0" Y="331.0" /> <Anchor Position="0.0" Shape="None" GraphId="f3a94" /> <Anchor Position="0.99" Shape="None" GraphId="f5828" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8857928" /> </Interaction> <Interaction GraphId="a2378"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="773.0" Y="516.0" GraphRef="ef242" RelX="0.0" RelY="1.0" /> <Point X="771.0" Y="549.0" GraphRef="ee910" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785213" /> </Interaction> <Interaction GraphId="a279f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2301.0" Y="888.0" GraphRef="e6653" RelX="-1.0" RelY="-0.02857142857142857" /> <Point X="2246.0" Y="898.0" GraphRef="e354a" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876484" /> </Interaction> <Interaction GraphId="a27bb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="730.0" Y="331.0" GraphRef="f5828" RelX="-0.42999999999995" RelY="0.8100000000000023" /> <Point X="711.0" Y="334.0" GraphRef="d846b" RelX="-0.010101010101010102" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8857928" /> </Interaction> <Interaction GraphId="a2a3d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3430.0" Y="900.0" GraphRef="c85bd" RelX="0.0" RelY="0.9099999999999682" /> <Point X="3430.0" Y="903.0" GraphRef="b86aa" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266303" /> </Interaction> <Interaction GraphId="a2aa6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3793.0" Y="654.0" GraphRef="d488e" RelX="0.2199999999997999" RelY="-0.6000000000000227" /> <Point X="3686.0" Y="487.0" GraphRef="e97ed" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264689" /> </Interaction> <Interaction GraphId="a2cac"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1676.0" Y="681.0" GraphRef="bafdc" RelX="0.75" RelY="0.009999999999990905" /> <Point X="1679.0" Y="681.0" GraphRef="de7c9" RelX="-1.0" RelY="-0.0196078431372549" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174739" /> </Interaction> <Interaction GraphId="a2db4"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2865.0" Y="271.0" GraphRef="a63a0" RelX="0.9753086419753086" RelY="0.0" /> <Point X="2898.0" Y="224.0" GraphRef="f0fd2" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682084" /> </Interaction> <Interaction GraphId="a2dd6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2056.0" Y="828.0" GraphRef="e10a6" RelX="-1.0" RelY="0.0" /> <Point X="2016.0" Y="828.0" GraphRef="bc5c3" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876696" /> </Interaction> <Interaction GraphId="a38df"> <Comment Source="Reactome">Lipoprotein lipase dimers (LPL:LPL) are tethered to heparan sulfate proteoglycans (HSPG) at endothelial cell surfaces (Fernandez-Borja et al. 1996; Peterson et al. 1992). Both syndecan 1 (Rosenberg et al. 1997) and perlecan (Goldberg 1996) HSPG molecules are capable of tethering LPL. The LPL enzyme catalyzes the hydrolysis and release of triacylglycerols (TG) associated with circulating chylomicrons to leave a CM remnant (CR). This reaction is annotated here as causing the hydrolysis and release of 50 molecules of TG. In vivo, the number is much larger, and TG depletion probably occurs in the course of multiple encounters between a chylomicron and endothelial LPL. This reaction is strongly activated by chylomicron-associated apo C-II protein both in vivo and in vitro (Jackson et al. 1986). Chylomicron-associated apoC-II protein inhibits LPL activity in vitro (Brown and Baginsky 1972), and recent studies have indicated a positive regulatory role for apoA-5 protein, though its molecular mechanism of action remains unclear (Marcais et al. 2005; Merkel and Heeren 2005). CRs can then be taken up by liver parenchymal cells in two ways; 1) directly by the LDL receptor or 2) apoE/HSPG-directed uptake by LDL receptor-related proteins.</Comment> <BiopaxRef>b48</BiopaxRef> <BiopaxRef>abd</BiopaxRef> <BiopaxRef>a14</BiopaxRef> <BiopaxRef>cc6</BiopaxRef> <BiopaxRef>c89</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1390.0" Y="439.0" /> <Point X="1208.0" Y="636.0" /> <Anchor Position="0.0" Shape="None" GraphId="b0982" /> <Anchor Position="0.99" Shape="None" GraphId="f1f1d" /> <Anchor Position="0.5" Shape="None" GraphId="bdf13" /> <Anchor Position="0.5" Shape="None" GraphId="b0b1c" /> <Anchor Position="0.5" Shape="None" GraphId="decb1" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174757" /> </Interaction> <Interaction GraphId="a3a19"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3642.0" Y="302.0" GraphRef="e9c44" RelX="0.5799999999999272" RelY="0.36000000000001364" /> <Point X="3688.0" Y="267.0" GraphRef="e6a79" RelX="-0.037037037037037035" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216723" /> </Interaction> <Interaction GraphId="a4319"> <Comment Source="Reactome">The E3 ubiquitin-protein ligase (MYLIP, aka IDOL) mediates the ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. It acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating degradation of LDLR (Hong et al. 2010). Despite some similarities, the MYLIP and PCSK9 ubiquitination pathways for controlling (V)LDLR abundance appear to be independent of each other. MYLIP is a transcriptional target of liver X receptors (NR1H2 and NR1H3), which can increase MYLIP expression and hence decerease (V)LDLR levels (Zelcer et al. 2009, Hong et al. 2010, Sorrentino &amp; Zelcer 2010, Zhang et al. 2012).</Comment> <BiopaxRef>a69</BiopaxRef> <BiopaxRef>c41</BiopaxRef> <BiopaxRef>f4e</BiopaxRef> <BiopaxRef>bca</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3253.0" Y="1330.0" /> <Point X="3254.0" Y="1397.0" /> <Anchor Position="0.0" Shape="None" GraphId="d9163" /> <Anchor Position="0.99" Shape="None" GraphId="ad31e" /> <Anchor Position="0.5" Shape="None" GraphId="a7ee4" /> <Anchor Position="0.5" Shape="None" GraphId="f3d87" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8854628" /> </Interaction> <Interaction GraphId="a4362"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1548.0" Y="425.0" GraphRef="a397e" RelX="-0.7999999999999545" RelY="0.009999999999990905" /> <Point X="1487.0" Y="479.0" GraphRef="a5beb" RelX="0.9726027397260274" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174660" /> </Interaction> <Interaction GraphId="a4a52"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3512.0" Y="752.0" GraphRef="ca26c" RelX="0.9733333333333334" RelY="-0.030303030303030304" /> <Point X="3549.0" Y="846.0" GraphRef="c30d5" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266315" /> </Interaction> <Interaction GraphId="a4def"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="771.0" Y="104.0" GraphRef="e3cd3" RelX="-1.0" RelY="-0.030303030303030304" /> <Point X="708.0" Y="151.0" GraphRef="d8900" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784861" /> </Interaction> <Interaction GraphId="a4f73"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3440.0" Y="627.0" GraphRef="e0311" RelX="0.6199999999998909" RelY="0.0" /> <Point X="3490.0" Y="627.0" GraphRef="e1471" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266082" /> </Interaction> <Interaction GraphId="a5c44"> <Comment Source="Reactome">The human lipolysis-stimulated lipoprotein receptor (LSR, LISCH) probably plays a role in the clearance of triglyceride-rich lipoproteins from blood, allowing their subsequent uptake into cells. Its affinity is highest for those lipoproteins most susceptible to lipolysis such as chylomicrons, LDL and VLDL. Human LSR function is inferred from mouse Lsr expression, functional and gene silencing studies (Yen et al. 1999, Mesli et al. 2004, Yen et al. 2008). Lsr inactivation in mice during embryogenesis resulted in death and indicated expression of Lsr was critical for liver and embryonic development (Mesli et al. 2004). This reaction shows LSR binding VLDL.</Comment> <BiopaxRef>bb5</BiopaxRef> <BiopaxRef>be9</BiopaxRef> <BiopaxRef>a90</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2449.0" Y="536.0" /> <Point X="2509.0" Y="535.0" /> <Anchor Position="0.0" Shape="None" GraphId="b3759" /> <Anchor Position="0.99" Shape="None" GraphId="d02af" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8933292" /> </Interaction> <Interaction GraphId="a6088"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3438.0" Y="752.0" GraphRef="ca26c" RelX="-1.0" RelY="-0.030303030303030304" /> <Point X="3250.0" Y="728.0" GraphRef="bc6d8" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266328" /> </Interaction> <Interaction GraphId="a65b6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1479.0" Y="983.0" GraphRef="b37cc" RelX="-0.009345794392523364" RelY="0.9636363636363636" /> <Point 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<Point X="2101.0" Y="80.0" GraphRef="e4361" RelX="0.0" RelY="1.0" /> <Point X="2067.0" Y="120.0" GraphRef="f5c9b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866329" /> </Interaction> <Interaction GraphId="a7942"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2148.0" Y="537.0" GraphRef="a571f" RelX="0.9636363636363636" RelY="-0.02702702702702703" /> <Point X="2168.0" Y="537.0" GraphRef="b77ee" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8854408" /> </Interaction> <Interaction GraphId="a7ab8"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1467.0" Y="636.0" GraphRef="b23fd" RelX="0.7100000000000364" RelY="0.009999999999990905" /> <Point X="1515.0" Y="610.0" GraphRef="fa531" RelX="-1.0" RelY="-0.015873015873015872" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174690" /> </Interaction> <Interaction GraphId="a85f3"> <Graphics 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<Interaction GraphId="a90c2"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2535.0" Y="1019.0" GraphRef="f6715" RelX="-0.012658227848101266" RelY="1.0" /> <Point X="2535.0" Y="1022.0" GraphRef="d02ae" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171106" /> </Interaction> <Interaction GraphId="a9150"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1306.0" Y="73.0" GraphRef="b4b88" RelX="0.0" RelY="1.0" /> <Point X="1267.0" Y="116.0" GraphRef="a9b0e" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174786" /> </Interaction> <Interaction GraphId="a957a"> <Comment Source="Reactome">Cyclic AMP-responsive element-binding protein 3-like protein 3 (CREB3L3) is a transcription factor that is highly and selectively expressed in liver and small intestine. This protein is produced as an ER-localized type II transmembrane glycoprotein that is converted into the mature nuclear form (the N-terminal portion) by sequence specific proteases, membrane-bound transcription factor site-1 proteases 1 and 2 (MBTPS1 and 2) (Marschner et al. 2011, Oeffner et al. 2009). CREB3L3 is a downstream target gene of hepatocyte nuclear factor 4a (HNF-4a), which plays a critical role in hepatocyte differentiation and liver function. Ablation of HNF-4a abolished CREB-H mRNA expression in the liver, but not in the small intestine, suggesting an essential role of HNF-4a in hepatic CREB-H expression.</Comment> <BiopaxRef>adb</BiopaxRef> <BiopaxRef>f37</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="413.0" Y="133.0" /> <Point X="413.0" Y="186.0" /> <Anchor Position="0.0" Shape="None" GraphId="d4518" /> <Anchor Position="0.99" Shape="None" GraphId="bf29b" /> <Anchor Position="0.5" Shape="None" GraphId="bf377" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784620" /> </Interaction> <Interaction GraphId="a95c7"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2616.0" Y="1287.0" GraphRef="f5aa0" RelX="-1.0" RelY="-0.02702702702702703" /> <Point X="2613.0" Y="1293.0" GraphRef="b3357" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784729" /> </Interaction> <Interaction GraphId="a96e8"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1223.0" Y="58.0" GraphRef="c753b" RelX="1.0" RelY="0.0" /> <Point X="1267.0" Y="116.0" GraphRef="a9b0e" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174786" /> </Interaction> <Interaction GraphId="a9cbb"> <Comment Source="Reactome">In macrophages, the hydrolysis of cholesteryl esters (CHESTs) is the rate-limiting step in the removal of free cholesterol (CHOL) from these cells. CHOL is transported via transport vesicles and can be used for cellular functions or removed from the cell by ABCA1 to create new HDL particles. Accumulation of CHESTs in macrophage foam cells is key to atherosclerotic plaque formation (Dubland &amp; Francis 2015). Exit from lysosomes of CHOL derived from the hydrolysis of CHESTs in low-density lipoproteins (LDLs) requires the concerted effort of two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. In the second step, NPC2 transfers CHOL to the CHOL-binding pocket of the N-terminal domain of NPC1 (Infante et al. 2008). During the transfer of CHOL from NPC2 to NPC1, the orientation of CHOL is reversed, allowing insertion of its isooctyl side chain into the outer lysosomal membrane (Kwon et al. 2009).</Comment> <BiopaxRef>e77</BiopaxRef> <BiopaxRef>ad9</BiopaxRef> <BiopaxRef>b3e</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2246.0" Y="898.0" /> <Point X="2246.0" Y="959.0" /> <Anchor Position="0.0" Shape="None" GraphId="e354a" /> <Anchor Position="0.99" Shape="None" GraphId="e4a66" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876484" /> </Interaction> <Interaction GraphId="a9d4d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1204.0" Y="523.0" GraphRef="b5c9a" RelX="-1.2181818181818183" RelY="-0.043478260869565216" /> <Point X="1208.0" Y="579.0" GraphRef="decb1" RelX="-91.0" RelY="41.5" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174757" /> </Interaction> <Interaction GraphId="aa049"> <Comment Source="Reactome">As an alternative to LDLR-mediated uptake and degradation, a LDL particle can bind a single molecule of LPA (apolipoprotein A), forming a Lp(a) lipoprotein particle. Although LPA is synthesized in liver cells, LPA - LDL binding appears to occur primarily extracellularly in vivo, on the hepatocyte surface or in the blood (Lobentanz et al. 1998). Lp(a) particles are relatively long-lived, with a half-life in human plasma of three to four days (Krempler et al. 1980), and the molecular mechanism of their clearance from the blood in vivo remains obscure. Lp(a) particles are of clinical interest because elevated levels of them are correlated with elevated risk of coronary heart disease (reviewed by Marcovina et al. 2003).</Comment> <BiopaxRef>c8f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2685.0" Y="621.0" /> <Point X="2686.0" Y="664.0" /> <Anchor Position="0.0" Shape="None" GraphId="f0949" /> <Anchor Position="0.99" Shape="None" GraphId="a5046" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-176879" /> </Interaction> <Interaction GraphId="aa1db"> <Comment Source="Reactome">Triacylglycerol (TG)-depleted chylomicrons transfer A and C apoproteins to spherical (mature) HDL, generating chylomicron remnants (Havel and Kane 2001). This transfer is arbitrarily annotated here as involving one molecule of each apolipoprotein. The molecular difference that enables nascent chylomicrons to accept apolipoproteins from sperical HDL and TG-depleted chylomicrons to donate them is unclear.</Comment> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1396.0" Y="635.0" /> <Point X="1467.0" Y="636.0" /> <Anchor Position="0.0" Shape="None" GraphId="ac3ca" /> <Anchor Position="0.99" Shape="None" GraphId="b23fd" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174690" /> </Interaction> <Interaction GraphId="aa20d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1451.0" Y="496.0" GraphRef="a5beb" RelX="-0.0136986301369863" RelY="1.0" /> <Point X="1396.0" Y="635.0" GraphRef="ac3ca" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174690" /> </Interaction> <Interaction GraphId="aa26c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3223.0" Y="272.0" GraphRef="dc99a" RelX="-0.012345679012345678" 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LineThickness="1.0"> <Point X="3254.0" Y="1397.0" GraphRef="ad31e" RelX="0.010000000000218279" RelY="0.6700000000000728" /> <Point X="3254.0" Y="1400.0" GraphRef="fc84a" RelX="-0.013333333333333334" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8854628" /> </Interaction> <Interaction GraphId="ab18b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3620.0" Y="222.0" GraphRef="ce5fb" RelX="0.0" RelY="1.0" /> <Point X="3583.0" Y="321.0" GraphRef="fa2ab" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216757" /> </Interaction> <Interaction GraphId="ab359"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2658.0" Y="842.0" GraphRef="dff99" RelX="0.0" RelY="1.0" /> <Point X="2657.0" Y="845.0" GraphRef="d14ea" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171141" /> </Interaction> <Interaction GraphId="ab43d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2170.0" Y="79.0" GraphRef="b3836" RelX="1.0300000000002" RelY="-0.4099999999999966" /> <Point X="2186.0" Y="76.0" GraphRef="ddda8" RelX="-0.015384615384615385" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866329" /> </Interaction> <Interaction GraphId="ab665"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3878.0" Y="656.0" GraphRef="d9414" RelX="-0.010000000000218279" RelY="0.7300000000000182" /> <Point X="3913.0" Y="671.0" GraphRef="ef62a" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264695" /> </Interaction> <Interaction GraphId="abdb3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1208.0" Y="636.0" GraphRef="f1f1d" RelX="-1.8199999999999363" RelY="1.9700000000000273" /> <Point X="1159.0" Y="664.0" GraphRef="a627f" RelX="0.9591836734693877" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174757" /> </Interaction> <Interaction GraphId="ac24f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3251.0" Y="1214.0" GraphRef="cbc58" RelX="0.0" RelY="-0.5399999999999636" /> <Point X="3251.0" Y="1211.0" GraphRef="de927" RelX="-0.015384615384615385" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8855111" /> </Interaction> <Interaction GraphId="ac499"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1200.0" Y="177.0" GraphRef="ef746" RelX="-0.012345679012345678" RelY="0.9354838709677419" /> <Point X="1200.0" Y="181.0" GraphRef="b7dbf" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174731" /> </Interaction> <Interaction GraphId="ac771"> <Comment Source="Reactome">Circulating nascent chylomicrons acquire copies of apolipoproteins C-II, C-III, and E from circulating spherical (mature) high-density lipoprotein particles, becoming mature chylomicrons (Havel et al. 1973; Bisgaier and Glickman 1983). Here, this interaction is annotated to involve the transfer of a single copy of each lipoprotein, but a mature chylomicron in fact contains approximately 25 copies of apolipoprotein E and 180 copies of C apolipoproteins (Bhattacharya and Redgrave 1981).</Comment> <BiopaxRef>c84</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1628.0" Y="424.0" /> <Point X="1548.0" Y="425.0" /> <Anchor Position="0.0" Shape="None" GraphId="ded85" /> <Anchor Position="0.99" Shape="None" GraphId="a397e" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174660" /> </Interaction> <Interaction GraphId="ac7eb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="154.0" Y="157.0" GraphRef="ed487" RelX="-0.007407407407407408" RelY="0.9591836734693877" /> <Point X="154.0" Y="164.0" GraphRef="b23c5" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784622" /> </Interaction> <Interaction GraphId="ac9ae"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="154.0" Y="297.0" GraphRef="c647a" RelX="0.0" RelY="1.330000000000041" /> <Point X="155.0" Y="303.0" GraphRef="f599c" RelX="-0.007751937984496124" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784622" /> </Interaction> <Interaction GraphId="acbe7"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3538.0" Y="627.0" GraphRef="e1471" RelX="0.9591836734693877" RelY="0.0" /> <Point X="3638.0" Y="643.0" GraphRef="e23fb" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266089" /> </Interaction> <Interaction GraphId="ad28c"> <Comment Source="Reactome">Extracellular discoidal HDL particles interact with cholesterol-rich membrane patches formed through the action of ABCG1 (Vaughan and Oram 2005). In the body this reaction is a key step in the process of reverse cholesterol transport, by which excess cholesterol is recovered from cells such a macrophages and transported ultimately to the liver. At a molecular level, it is one of the steps in the transformation of discoidal (small nascent) HDL particles into spherical ones, distinct from the similar reaction in which cholesterol is transferred to lipid-free apoA-I protein (Oram and Vaughan 2006; Kontush and Chapman 2006).</Comment> <BiopaxRef>a04</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3638.0" Y="643.0" /> <Point X="3638.0" Y="713.0" /> <Anchor Position="0.0" Shape="None" GraphId="e23fb" /> <Anchor Position="0.99" Shape="None" GraphId="af643" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266089" /> </Interaction> <Interaction GraphId="ad307"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3741.0" Y="1153.0" GraphRef="b4f2d" RelX="-0.6700000000000728" RelY="0.0" /> <Point X="3737.0" Y="1153.0" GraphRef="ce4f4" RelX="0.9692307692307692" RelY="-0.030303030303030304" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8858252" /> </Interaction> <Interaction GraphId="ad347"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3514.0" Y="642.0" GraphRef="e1471" RelX="-0.02040816326530612" RelY="1.0" /> <Point X="3555.0" Y="753.0" GraphRef="aa5b5" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266299" /> </Interaction> <Interaction GraphId="ad4f2"> <Comment Source="Reactome">The PCSK9:LDLR:Clathrin-coated vesicle is internalized to endosomes and, after that, to lysosomes where PCSK9 and LDLR are degraded (Wang et al. 2012).</Comment> <BiopaxRef>d3b</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2613.0" Y="1293.0" /> <Point X="2447.0" Y="1313.0" /> <Anchor Position="0.0" Shape="None" GraphId="b3357" /> <Anchor Position="0.99" Shape="None" GraphId="af266" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784729" /> </Interaction> <Interaction GraphId="ad6e7"> <Comment Source="Reactome">Phospholipid (PL) and triacylglycerol (TG) associate with the apo B-48 polypeptide as it is translated. This process is mediated by MTP (microsomal triacylglycerol transfer protein) in the form of a MTP:PDI (protein disulfide isomerase) heterodimer. MTP in vitro binds small amounts of PL and TG (annotated here as as one molecule of each) and efficiently transfers the bound lipid between membranes (Atzel and Wetterau 1994). In vivo, MTP:PDI directly interacts with apoB-48 polypeptide (Wu et al. 1996), and is thought to transfer lipid from the endoplasmic reticulum membrane to nascent apoB-48. While some of the molecular details of MTP function remain unclear, this function is clearly essential in vivo, as patients who lack MTP cannot produce chylomicrons (e.g., Wetterau et al. 1992; Narcisi et al. 1995).</Comment> <BiopaxRef>dc2</BiopaxRef> <BiopaxRef>bf6</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1267.0" Y="116.0" /> <Point X="1399.0" Y="79.0" /> <Anchor Position="0.0" Shape="None" GraphId="a9b0e" /> <Anchor Position="0.99" Shape="None" GraphId="cde76" /> <Anchor Position="0.5" Shape="None" GraphId="d9718" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174786" /> </Interaction> <Interaction GraphId="adec5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2977.0" Y="225.0" GraphRef="cbbc7" RelX="0.7899999999999636" RelY="0.009999999999990905" /> <Point X="3020.0" Y="207.0" GraphRef="aa304" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682084" /> </Interaction> <Interaction GraphId="ae69a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3656.0" Y="353.0" GraphRef="f84ea" RelX="0.7300000000000182" RelY="0.3199999999999932" /> <Point X="3688.0" Y="267.0" GraphRef="e6a79" RelX="-0.037037037037037035" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216757" /> </Interaction> <Interaction GraphId="aedf2"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2681.0" Y="845.0" GraphRef="dabbb" RelX="-1.0199999999999818" RelY="-0.8500000000000227" /> <Point X="2658.0" Y="842.0" GraphRef="dff99" RelX="0.0" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171122" /> </Interaction> <Interaction GraphId="af150"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3569.0" Y="820.0" GraphRef="bee6b" RelX="0.11000000000012733" RelY="-1.0" /> <Point X="3512.0" Y="752.0" GraphRef="ca26c" RelX="0.9733333333333334" RelY="-0.030303030303030304" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266310" /> </Interaction> <Interaction GraphId="af3cc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3689.0" Y="311.0" GraphRef="b4826" RelX="-1.0" RelY="0.0" /> <Point X="3637.0" Y="413.0" GraphRef="bcb3d" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216756" /> </Interaction> <Interaction GraphId="af488"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1907.0" Y="1062.0" GraphRef="dd476" RelX="0.9636363636363636" RelY="0.0" /> <Point X="1964.0" Y="1062.0" GraphRef="c955a" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6813720" /> </Interaction> <Interaction GraphId="afbdd"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1598.0" Y="914.0" GraphRef="ab012" RelX="0.0" RelY="1.0" /> <Point X="1598.0" Y="917.0" GraphRef="cab49" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174706" /> </Interaction> <Interaction GraphId="b0553"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1362.0" Y="263.0" GraphRef="a51f6" RelX="1.0" RelY="0.0" /> <Point X="1609.0" Y="109.0" GraphRef="a3540" RelX="14.0" RelY="-0.5" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174741" /> </Interaction> <Interaction GraphId="b05df"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3737.0" Y="311.0" GraphRef="b4826" RelX="0.9591836734693877" RelY="0.0" /> <Point X="3779.0" Y="385.0" GraphRef="dd713" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349657" /> </Interaction> <Interaction GraphId="b0d67"> <Comment Source="Reactome">The LCAT:discoidal HDL complex dissociates reversibly to yield LCAT and a discoidal HDL particle.</Comment> <BiopaxRef>da3</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3771.0" Y="714.0" /> <Point X="3793.0" Y="654.0" /> <Anchor Position="0.0" Shape="None" GraphId="ee432" /> <Anchor Position="0.99" Shape="None" GraphId="d488e" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264689" /> </Interaction> <Interaction GraphId="b105a"> <Comment Source="Reactome">LDLR that engage PCSK9 at the cell membrane are internalized via the canonical clathrin-dependent endocytic machinery (Wang et al. 2012). This complex is routed to lysosomes via a pathway that does not require ubiquitination of the cytoplasmic tail of the receptor and does not involve the proteasomal or autophagy pathways. 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This binding is mediated by the apoprotein B-100 component of the LDL particle, which binds LDLR with 1:1 stoichiometry (van Driel et al. 1989).</Comment> <BiopaxRef>a59</BiopaxRef> <BiopaxRef>ab4</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2783.0" Y="930.0" /> <Point X="2681.0" Y="845.0" /> <Anchor Position="0.0" Shape="None" GraphId="aaf3b" /> <Anchor Position="0.99" Shape="None" GraphId="dabbb" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171122" /> </Interaction> <Interaction GraphId="b3021"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="858.0" Y="230.0" GraphRef="f83d5" RelX="0.9400000000000546" RelY="-1.1000000000000227" /> <Point X="733.0" Y="102.0" GraphRef="a53c6" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784628" /> </Interaction> <Interaction GraphId="b4369"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3834.0" Y="613.0" GraphRef="e8113" RelX="1.0" RelY="0.0" /> <Point X="3877.0" Y="614.0" GraphRef="bbe4e" RelX="-1.5" RelY="-5.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264695" /> </Interaction> <Interaction GraphId="b442d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2306.0" Y="436.0" GraphRef="c320e" RelX="1.0" RelY="0.0" /> <Point X="2449.0" Y="536.0" GraphRef="b3759" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8933292" /> </Interaction> <Interaction GraphId="b4800"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2657.0" Y="1022.0" GraphRef="b47db" RelX="-0.022222222222222223" RelY="1.0" /> <Point X="2657.0" Y="1056.0" GraphRef="e1b9e" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784734" /> </Interaction> <Interaction GraphId="b48a5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2045.0" Y="1152.0" GraphRef="f2ca2" RelX="1.2200000000000273" RelY="0.009999999999990905" /> <Point X="2046.0" Y="1118.0" GraphRef="cc8c7" RelX="0.971830985915493" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8937442" /> </Interaction> <Interaction GraphId="b50b2"> <Comment Source="Reactome">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.</Comment> <BiopaxRef>d42</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1672.0" Y="812.0" /> <Point X="1646.0" Y="863.0" /> <Anchor Position="0.0" Shape="None" GraphId="f34f9" /> <Anchor Position="0.99" Shape="None" GraphId="e556f" /> <Anchor Position="0.5" Shape="None" GraphId="c4e9c" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174657" /> </Interaction> <Interaction GraphId="b526c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2526.0" Y="120.0" GraphRef="ee959" RelX="-0.02127659574468085" RelY="1.0" /> <Point X="2526.0" Y="123.0" GraphRef="f43ee" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866327" /> </Interaction> <Interaction GraphId="b604f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3253.0" Y="1304.0" GraphRef="a0b47" RelX="-0.017543859649122806" RelY="-1.0" /> <Point X="3251.0" Y="1268.0" GraphRef="b3f18" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8855111" /> </Interaction> <Interaction GraphId="b64b2"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3355.0" Y="337.0" GraphRef="b6a22" RelX="0.0" RelY="1.0" /> <Point X="3382.0" Y="365.0" GraphRef="eb655" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216727" /> </Interaction> <Interaction GraphId="b6927"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="324.0" Y="211.0" GraphRef="f8b89" RelX="-1.0" RelY="-0.030303030303030304" /> <Point X="321.0" Y="209.0" GraphRef="d235a" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784648" /> </Interaction> <Interaction GraphId="b69c5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="753.0" Y="220.0" GraphRef="b6366" RelX="1.0" RelY="0.0" /> <Point X="773.0" Y="250.0" GraphRef="f3a94" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8857928" /> </Interaction> <Interaction GraphId="b7724"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3901.0" Y="937.0" GraphRef="a2738" RelX="0.9699999999997999" RelY="0.0" /> <Point X="3920.0" Y="982.0" GraphRef="ce135" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8980228" /> </Interaction> <Interaction GraphId="b7dc3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="857.0" Y="371.0" GraphRef="bf040" RelX="-1.0" RelY="0.0" /> <Point X="861.0" Y="313.0" GraphRef="e4ae6" RelX="50.0" RelY="28.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784628" /> </Interaction> <Interaction GraphId="b7fb0"> <Comment Source="Reactome">Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of plasma cholesterol homeostasis by binding to low-density lipid receptor family members and promoting their degradation in lysosomes (Poirier et al. 2008). In mice, it was observed that circulating PCSK9 can regulate VLDLR protein levels in adipose tissue and thereby, fat accumulation. The absence of PCSK9 led to an increase in lipid uptake resulting in adipocyte hypertrophy which was LDLR-independent (Roubtsova et al. 2011). Whether increased fat deposition also occurs in humans lacking functional PCSK9 remains to be elucidated.</Comment> <BiopaxRef>b1c</BiopaxRef> <BiopaxRef>b6b</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3251.0" Y="1268.0" /> <Point X="3251.0" Y="1214.0" /> <Anchor Position="0.0" Shape="None" GraphId="b3f18" /> <Anchor Position="0.99" Shape="None" GraphId="cbc58" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8855111" /> </Interaction> <Interaction GraphId="b886a"> <Comment Source="Reactome">The human lipolysis-stimulated lipoprotein receptor (LSR, LISCH) probably plays a role in the clearance of triglyceride-rich lipoproteins from blood, allowing their subsequent uptake into cells. Its affinity is highest for those lipoproteins most susceptible to lipolysis such as chylomicrons, LDL and VLDL. Human LSR function is inferred from mouse Lsr expression, functional and gene silencing studies (Yen et al. 1999, Mesli et al. 2004, Yen et al. 2008). Lsr inactivation in mice during embryogenesis resulted in death and indicated expression of Lsr was critical for liver and embryonic development (Mesli et al. 2004). This reaction shows LSR binding LDL.</Comment> <BiopaxRef>bb5</BiopaxRef> <BiopaxRef>be9</BiopaxRef> <BiopaxRef>a90</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2512.0" Y="759.0" /> <Point X="2455.0" Y="794.0" /> <Anchor Position="0.0" Shape="None" GraphId="c7893" /> <Anchor Position="0.99" Shape="None" GraphId="db910" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8933258" /> </Interaction> <Interaction GraphId="b8cbc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="743.0" Y="275.0" GraphRef="de1dd" RelX="0.9692307692307692" RelY="0.0" /> <Point X="773.0" Y="250.0" GraphRef="f3a94" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8857928" /> </Interaction> <Interaction GraphId="b8db1"> <Comment Source="Reactome">LDL:LDLR complexes move rapidly from clathrin-coated vesicles to endosomes (Goldstein et al. 1979).</Comment> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2565.0" Y="924.0" /> <Point X="2535.0" Y="980.0" /> <Anchor Position="0.0" Shape="None" GraphId="fe889" /> <Anchor Position="0.99" Shape="None" GraphId="a974d" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171059" /> </Interaction> <Interaction GraphId="b9085"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2994.0" Y="619.0" GraphRef="a06b9" RelX="0.6999999999998181" RelY="0.0" /> <Point X="3028.0" Y="579.0" GraphRef="da826" RelX="-1.0" RelY="-0.02702702702702703" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266350" /> </Interaction> <Interaction GraphId="b92f1"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2763.0" Y="621.0" GraphRef="e64c0" RelX="-1.0" RelY="-0.05263157894736842" /> <Point X="2512.0" Y="759.0" GraphRef="c7893" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8933258" /> </Interaction> <Interaction GraphId="b96b0"> <Comment Source="Reactome">LPL enzyme is catalytically active as a dimer composed of two glycosylated subunits of LPL connected in a head-to-tail arrangement by non-covalent interactions. It is synthesised in adipocytes and exported to the luminal side of the capillary endothelium where it binds heparan sulfate proteoglycan (HSPG), serving as an membrane anchor for the LPL dimer (Lookene et al. 1997, Berryman &amp; Bensadoun 1995).</Comment> <BiopaxRef>f46</BiopaxRef> <BiopaxRef>aba</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="708.0" Y="151.0" /> <Point X="710.0" Y="197.0" /> <Anchor Position="0.0" Shape="None" GraphId="d8900" /> <Anchor Position="0.99" Shape="None" GraphId="a35c6" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784861" /> </Interaction> <Interaction GraphId="b9e4c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3656.0" Y="353.0" GraphRef="f84ea" RelX="0.7300000000000182" RelY="0.3199999999999932" /> <Point X="3650.0" Y="261.0" GraphRef="a4b1d" RelX="-0.024390243902439025" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216757" /> </Interaction> <Interaction GraphId="baf8b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3053.0" Y="1245.0" GraphRef="d7583" RelX="0.01999999999998181" RelY="0.5499999999999545" /> <Point X="3055.0" Y="1248.0" GraphRef="bdf3d" RelX="-0.012658227848101266" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8855130" /> </Interaction> <Interaction GraphId="bb2c7"> <Comment Source="Reactome">An extracellular spherical HDL particle binds to the plasma membrance-associated SR-BI receptor with high affinity (Murao et al. 1997). In the body SR-BI receptors are abundant on the surfaces of steroidogenic cells in the adrenal glands and gonads, and on hepatocytes. SR-BI thus appears to play a central role in cholesterol uptake for steroid hormone synthesis and for bile acid synthesis and cholesterol excretion (Rigotti et al. 2003; Silver and Tall 2001).</Comment> <BiopaxRef>df1</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3881.0" Y="1266.0" /> <Point X="3881.0" Y="1336.0" /> <Anchor Position="0.0" Shape="None" GraphId="d5fe0" /> <Anchor Position="0.99" Shape="None" GraphId="c744e" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349637" /> </Interaction> <Interaction GraphId="bb931"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2588.0" Y="921.0" GraphRef="e41ec" RelX="-0.0136986301369863" RelY="1.0" /> <Point X="2565.0" Y="924.0" GraphRef="fe889" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171059" /> </Interaction> <Interaction GraphId="bbabb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2424.0" Y="1105.0" GraphRef="c6daf" RelX="-0.6399999999998727" RelY="0.009999999999990905" /> <Point X="2421.0" Y="1106.0" GraphRef="aa0a7" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876366" /> </Interaction> <Interaction GraphId="bc0fa"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="918.0" Y="310.0" GraphRef="edf5d" RelX="-0.29411764705882354" RelY="4.714285714285714" /> <Point X="861.0" Y="313.0" GraphRef="b3f64" RelX="50.0" RelY="28.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784628" /> </Interaction> <Interaction GraphId="bc813"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2010.0" Y="65.0" GraphRef="d4c69" RelX="1.0" RelY="0.0" /> <Point X="2067.0" Y="120.0" GraphRef="f5c9b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866329" /> </Interaction> <Interaction GraphId="bcba1"> <Comment Source="Reactome">NCEH1 (neutral cholesterol ester hydrolase) hydrolyzes cholesterol esters to form cholesterol (CHOL) and free fatty acids (LCFA). In both humans (Igarashi et al. 2010a) and mice (Igarashi et al. 2010b, Okazaki et al. 2008, Sakai et al. 2014 ) NCEH1 associated with the endoplasmic reticulum membrane appears to play a major role in cholesterol ester hydrolysis in macrophages. Free CHOL is transported via transport vesicles and can be used for cellular functions or removed from the cell by ABCA1 to create new HDL particles.</Comment> <BiopaxRef>c26</BiopaxRef> <BiopaxRef>e0f</BiopaxRef> <BiopaxRef>cde</BiopaxRef> <BiopaxRef>bc8</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1964.0" Y="1062.0" /> <Point X="2002.0" Y="1063.0" /> <Anchor Position="0.0" Shape="None" GraphId="c955a" /> <Anchor Position="0.99" Shape="None" GraphId="c8b67" /> <Anchor Position="0.5" Shape="None" GraphId="a54d9" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6813720" /> </Interaction> <Interaction GraphId="bd2f1"> <Comment Source="Reactome">The hepatic triacylglycerol lipase dimer (LIPC dimer) requires binding to heparin for stability of the homodimer (Ben-Zeev et al. 2011).</Comment> <BiopaxRef>d4f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="771.0" Y="549.0" /> <Point X="772.0" Y="618.0" /> <Anchor Position="0.0" Shape="None" GraphId="ee910" /> <Anchor Position="0.99" Shape="None" GraphId="b9040" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785213" /> </Interaction> <Interaction GraphId="be010"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1407.0" Y="436.0" GraphRef="d9660" RelX="-0.011764705882352941" RelY="1.0" /> <Point X="1390.0" Y="439.0" GraphRef="b0982" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174757" /> </Interaction> <Interaction GraphId="be868"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3328.0" Y="413.0" GraphRef="bec1e" RelX="1.2800000000002" RelY="-0.009999999999990905" /> <Point X="3331.0" Y="413.0" GraphRef="b5ee4" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264758" /> </Interaction> <Interaction GraphId="be896"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3943.0" Y="813.0" GraphRef="ea875" RelX="0.0" RelY="0.6499999999999773" /> <Point X="3944.0" Y="816.0" GraphRef="e9fad" RelX="-0.009523809523809525" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264679" /> </Interaction> <Interaction GraphId="beb5d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2296.0" Y="1104.0" GraphRef="abe89" RelX="-0.7199999999997999" RelY="-0.009999999999990905" /> <Point X="2308.0" Y="1048.0" GraphRef="f50e2" RelX="-0.0196078431372549" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8865667" /> </Interaction> <Interaction GraphId="becb1"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3974.0" Y="730.0" GraphRef="def39" RelX="-1.0" RelY="-0.04" /> <Point X="3943.0" Y="748.0" GraphRef="e888c" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264679" /> </Interaction> <Interaction GraphId="bed96"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3798.0" Y="1480.0" GraphRef="a5a9a" RelX="-0.8400000000001455" RelY="0.8900000000001" /> <Point X="3657.0" Y="1602.0" GraphRef="a3597" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349638" /> </Interaction> <Interaction GraphId="beee4"> <Comment Source="Reactome">Hepatic triacylglycerol lipase (LIPC, and lipoprotein lipase, LPL) are dimeric lipases (Hill et al. 1997) that hydrolyse triglycerides from circulating lipoproteins thereby playing important roles in lipoprotein remodeling and uptake. 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Consistent with the essential role of LPL in TG clearance, CREB3L3-deficient mice showed hypertriglyceridemia, associated with defective production of these apolipoproteins and decreased LPL activity.</Comment> <BiopaxRef>ca6</BiopaxRef> <BiopaxRef>b02</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="321.0" Y="209.0" /> <Point X="267.0" Y="209.0" /> <Anchor Position="0.0" Shape="None" GraphId="d235a" /> <Anchor Position="0.99" Shape="None" GraphId="ef687" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784648" /> </Interaction> <Interaction GraphId="c20b5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1725.0" Y="706.0" GraphRef="de7c9" RelX="-0.010752688172043012" RelY="0.9607843137254902" /> <Point X="1672.0" Y="812.0" GraphRef="f34f9" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174657" /> </Interaction> <Interaction GraphId="c26b3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3057.0" Y="763.0" GraphRef="d3be0" RelX="1.0" RelY="0.0" /> <Point X="3088.0" Y="802.0" GraphRef="e197d" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349404" /> </Interaction> <Interaction GraphId="c325a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2460.0" Y="393.0" GraphRef="ffb40" RelX="-1.0" RelY="0.0" /> <Point X="2440.0" Y="436.0" GraphRef="caa5a" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866321" /> </Interaction> <Interaction GraphId="c32a9"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1485.0" Y="196.0" GraphRef="b9e33" RelX="0.9692307692307692" RelY="-0.03225806451612903" /> <Point X="1541.0" Y="109.0" GraphRef="f2a75" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174741" /> </Interaction> <Interaction GraphId="c38a5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2231.0" Y="537.0" GraphRef="e9947" RelX="0.6300000000001091" RelY="0.0" /> <Point X="2234.0" Y="538.0" GraphRef="b981e" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8854408" /> </Interaction> <Interaction GraphId="c3b79"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2332.0" Y="909.0" GraphRef="b9a87" RelX="-0.010000000000218279" RelY="-0.6599999999999682" /> <Point X="2332.0" Y="905.0" GraphRef="e6653" RelX="0.0" RelY="0.9428571428571428" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876472" /> </Interaction> <Interaction GraphId="c3e0b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2350.0" Y="1319.0" GraphRef="cbfa8" RelX="-1.0" RelY="-0.02702702702702703" /> <Point X="2347.0" Y="1318.0" GraphRef="d3f3a" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784738" /> </Interaction> <Interaction GraphId="c3fa4"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2656.0" Y="1151.0" GraphRef="f6fe5" RelX="-0.010000000000218279" RelY="0.9500000000000455" /> <Point X="2656.0" Y="1154.0" GraphRef="e87ea" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784734" /> </Interaction> <Interaction GraphId="c46e6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2644.0" Y="1025.0" GraphRef="f2217" RelX="0.4299999999998363" RelY="-0.38000000000010914" /> <Point X="2657.0" Y="1022.0" GraphRef="b47db" RelX="-0.022222222222222223" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171087" /> </Interaction> <Interaction GraphId="c4c35"> <Comment Source="Reactome">LDLR that engage PCSK9 at the cell membrane are internalized via the canonical clathrin-dependent endocytic machinery (Wang et al. 2012). This complex is routed to lysosomes via a pathway that does not require ubiquitination of the cytoplasmic tail of the receptor and does not involve the proteasomal or autophagy pathways. The clathrin is required for the internalization of the LDLR-PCSK9 complex that forms on the cell surface.</Comment> <BiopaxRef>d3b</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2582.0" Y="1215.0" /> <Point X="2617.0" Y="1266.0" /> <Anchor Position="0.0" Shape="None" GraphId="b05b6" /> <Anchor Position="0.99" Shape="None" GraphId="daa85" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784735" /> </Interaction> <Interaction GraphId="c4c9c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3535.0" Y="242.0" GraphRef="e7df7" RelX="1.0" RelY="0.0" /> <Point X="3583.0" Y="321.0" GraphRef="fa2ab" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216757" /> </Interaction> <Interaction GraphId="c4d84"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1880.0" Y="1077.0" GraphRef="dd476" RelX="-0.01818181818181818" RelY="1.0" /> <Point X="1923.0" Y="1151.0" GraphRef="a8626" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8937442" /> </Interaction> <Interaction GraphId="c4e32"> <Comment Source="Reactome">Pre-beta HDL (lipid-poor apoA-I) interacts with phospholipid- and cholesterol-rich membrane patches formed through the action of ABCA1, binding these two lipids to form a discoidal (small nascent) HDL particle (HDL 3c - Kontush and Chapman 2006).</Comment> <BiopaxRef>d8c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3779.0" Y="385.0" /> <Point X="3661.0" Y="473.0" /> <Anchor Position="0.0" Shape="None" GraphId="dd713" /> <Anchor Position="0.99" Shape="None" GraphId="ebebc" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349657" /> </Interaction> <Interaction GraphId="c5058"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1479.0" Y="1147.0" GraphRef="c1e2a" RelX="0.0" RelY="0.5399999999999636" /> <Point X="1479.0" Y="1169.0" GraphRef="c04e0" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174624" /> </Interaction> <Interaction GraphId="c5276"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2926.0" Y="258.0" GraphRef="a9f77" RelX="0.0" RelY="-1.0" /> <Point X="2934.0" Y="225.0" GraphRef="c93a4" RelX="-3.5" RelY="0.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682084" /> </Interaction> <Interaction GraphId="c5357"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3544.0" Y="318.0" GraphRef="afb36" RelX="0.9809523809523809" RelY="-0.0196078431372549" /> <Point X="3614.0" Y="302.0" GraphRef="b6b4f" RelX="1.0" RelY="18.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216723" /> </Interaction> <Interaction GraphId="c5638"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1566.0" Y="725.0" GraphRef="e5792" RelX="-0.022222222222222223" RelY="-1.0" /> <Point X="1601.0" Y="680.0" GraphRef="b5921" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174739" /> </Interaction> <Interaction GraphId="c5803"> <Comment Source="Reactome">Very low-density lipoproteins (VLDLs) are produced in the liver to transport endogenous triglycerides, phospholipids, cholesterol, and cholesteryl esters in the hydrophilic environment of the bloodstream. They comprise triglycerides (50-60%), cholesterol (10-12%), cholesterol esters (4-6%), phospholipids (18-20%), and apolipoprotein B (8-12%). Of the protein content, two other apolipoproteins are constituents; apolipoprotein C-I (APOC around 20%) (Westerterp et al. 2007) and apolipoprotein C4 (APOC4, minor amount) (Kotite et al. 2003). After release from the liver, circulating VLDL particles can bind very low-density lipoprotein receptors (VLDLR) (Sakai et al. 1994) on extra-hepatic target cells and undergo endocytosis (Go &amp; Mani 2012). VLDL uptake by VLDLR represents a minor contribution towards VLDL metabolism. The majority of VLDL is catalysed by lipoprotein lipase (LPL) which hydrolyses TAGs from VLDL, converting it to intermediate-density lipoprotein (IDL). IDL can be further hydrolysed by hepatic lipase to cholesterol-rich low-density lipoprotein (LDL).&lt;br&gt;&lt;br&gt;VLDLR consists of five functional domains that resemble the LDL receptor. It is highly expressed in tissues that actively metabolise fatty acids as a source of energy. Binding of VLDLs to VLDLR appears to be inhibited by apolipoprotein C-I (APOC1), therby slowing the clearance of triglyceride-rich lipoproteins from the circulation (Westerterp et al. 2007). The APOE/C1/C4/C2 gene cluster is closely associated with plasma lipid levels, atherosclerotic plaque formation, and thereby implicated in the development of coronary artery disease and Alzheimer’s disease (Xu et al. 2015).</Comment> <BiopaxRef>bc3</BiopaxRef> <BiopaxRef>c7a</BiopaxRef> <BiopaxRef>f86</BiopaxRef> <BiopaxRef>d27</BiopaxRef> <BiopaxRef>c3c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1921.0" Y="537.0" /> <Point X="1988.0" Y="536.0" /> <Anchor Position="0.0" Shape="None" GraphId="ef678" /> <Anchor Position="0.99" Shape="None" GraphId="d56c2" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8854462" /> </Interaction> <Interaction GraphId="c5c20"> <Comment Source="Reactome">LDL receptors in the endosome membrane are quickly returned to the cell surface (Goldstein et al. 1979).</Comment> <BiopaxRef>a59</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2601.0" Y="1063.0" /> <Point 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Dimeric LPL is cleaved by several proprotein convertases. FURIN and proprotein convertase subtilisin/kexin type 6 (PCSK6 aka PACE4) can cleave LPL dimer, inactivating it, resulting in subsequent increase in plasma TG concentrations (Siezen et al. 1994, Bassi et al. 2000, Jin et al. 2005). Endogenous modulators of LPL are the angiopoietin-like proteins ANGPTL3 and ANGPTL4, which can bind transiently to LPL dimer, resulting in conversion of the enzyme from a catalytically active dimer to inactive, but still folded, monomers (Liu et al. 2010, Sukonina et al. 2006). ANGPTL4 regulates plasma triglyceride concentration via the inhibition of LPL (Dijk &amp; Kersten 2014). GWAS studies (Dewey et al. 2016, MIG and CARDIoGRAM Consortium 2016) show a strong correlation between inactivating ANGPTL4 mutants and lower levels of triglycerides and lower risk of coronary artery disease than non-carriers. 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GraphId="cd55d"> <Comment Source="Reactome">Newly synthesized apoB-48 that is not complexed with lipid is rapidly degraded (Dixon et al. 1991). 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Two molecules of lipid bind strongly to a molecule of albumin; an additional five molecules bind more weakly (Nakagawa and Nishida 1973). The fate of the complex in vivo is unclear. In vitro 2-lysophosphatidylcholine can be esterified with fatty acid to generate phosphatidylcholine. Such a process could replenish the phosphatidylcholine consumed by cholesterol esterification in HDL particles, but the extent to which it occurs in vivo is unclear (Nakagawa and Nishida 1973; Switzer and Eder 1965).</Comment> <BiopaxRef>b26</BiopaxRef> <BiopaxRef>ad5</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3943.0" Y="748.0" /> <Point X="3943.0" Y="813.0" /> <Anchor Position="0.0" Shape="None" GraphId="e888c" /> <Anchor Position="0.99" Shape="None" GraphId="ea875" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264679" /> </Interaction> <Interaction GraphId="cfa65"> <Comment Source="Reactome">LCAT (lecithin-cholesterol acyltransferase) associates strongly but reversibly with discoidal HDL particles (Jonas 2000).</Comment> <BiopaxRef>da3</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3762.0" Y="642.0" /> <Point X="3762.0" Y="714.0" /> <Anchor Position="0.0" Shape="None" GraphId="b1810" /> <Anchor Position="0.99" Shape="None" GraphId="c7f5b" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264678" /> </Interaction> <Interaction GraphId="cfb1a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2539.0" Y="794.0" GraphRef="b7295" RelX="-1.0" RelY="-0.02702702702702703" /> <Point X="2512.0" Y="759.0" GraphRef="c7893" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8933258" /> </Interaction> <Interaction GraphId="cfc6e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2685.0" Y="1044.0" GraphRef="d8d07" RelX="-1.0" RelY="0.0" /> <Point X="2657.0" Y="1056.0" GraphRef="e1b9e" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784734" /> </Interaction> <Interaction GraphId="d0085"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3882.0" Y="1387.0" GraphRef="d8989" RelX="0.0" RelY="0.9591836734693877" /> <Point X="3882.0" Y="1391.0" GraphRef="e1d16" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349638" /> </Interaction> <Interaction GraphId="d015c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3878.0" Y="656.0" GraphRef="d9414" RelX="-0.010000000000218279" RelY="0.7300000000000182" /> <Point X="3881.0" Y="702.0" GraphRef="f4356" RelX="-0.018867924528301886" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264695" /> </Interaction> <Interaction GraphId="d08a0"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3438.0" Y="752.0" GraphRef="ca26c" RelX="-1.0" RelY="-0.030303030303030304" /> <Point X="3088.0" Y="802.0" GraphRef="e197d" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349404" /> </Interaction> <Interaction GraphId="d08dc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2536.0" Y="1075.0" GraphRef="c3f67" RelX="0.010000000000218279" RelY="0.5299999999999727" /> <Point X="2521.0" Y="1104.0" GraphRef="d1046" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171106" /> </Interaction> <Interaction GraphId="d0eec"> <Comment Source="Reactome">Excess cellular cholesterol (CHOL) is esterified and stored as cholesteryl ester (CHEST). The conversion is catalysed by the ER membrane-residing sterol O-acyltransferases 1 and 2 (SOAT1 and SOAT 2, aka acyl-coenzyme A:cholesterol acyltransferase 1 and 2, ACAT1 and 2) (Chang et al. 1993, Oelkers et al. 1998, Lin et al. 1999). CHESTs are usually present at low levels in most cells but chronic accumulation of CHEST in macrophages causes these cells to appear foamy and is a characteristic of early stage atherosclerosis (Becker et al. 1994). The SOAT enzymes are being investigated as potential drug targets for atherosclerosis and for Alzheimer's disease (Chang et al. 2009). Alzheimer's disease is a prevalent neurodegenerative disease, characterised by a large extracellular accumulation of amyloid plaques, composed mainly of beta-amyloid peptide aggregates. Increases in free cholesterol in the membrane, which can be caused by inhibiting ACAT1, can lead to the decrease of amyloid precursor protein processing. 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This process is reversible but in the body proceeds in the direction annotated here. A model for the lipid exchange process has been proposed based on recent studies of the structure of CETP:lipid complexes (Qiu et al. 2007).</Comment> <BiopaxRef>cc5</BiopaxRef> <BiopaxRef>fab</BiopaxRef> <BiopaxRef>d7a</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3250.0" Y="728.0" /> <Point X="3251.0" Y="834.0" /> <Anchor Position="0.0" Shape="None" GraphId="bc6d8" /> <Anchor Position="0.99" Shape="None" GraphId="a8628" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266328" /> </Interaction> <Interaction GraphId="d35ab"> <Comment Source="Reactome">In an ATP-dependent reaction, ABCG1 mediates the movement of intracellular cholesterol to the extracellular face of the plasma membrane. In a tissue culture model system, the active form of ABCG1 is predominantly a tetramer (Vuaghan and Oram 2005). 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Cholesterol associated with cytosolic vesicles is a substrate for this reaction. Under physiologocal conditions, the active form of ABCA1 is predominantly a tetramer associated with apolipoprotein A-I (APOA1) (Denis et al. 2004, Vedhachalam et al. 2007). The number of lipid molecules transported per ATP consumed is not known.</Comment> <BiopaxRef>d54</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3583.0" Y="321.0" /> <Point X="3656.0" Y="353.0" /> <Anchor Position="0.0" Shape="None" GraphId="fa2ab" /> <Anchor Position="0.99" Shape="None" GraphId="f84ea" /> <Anchor Position="0.5" Shape="None" GraphId="bae1c" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216757" /> </Interaction> <Interaction GraphId="d66a9"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3798.0" Y="1480.0" GraphRef="a5a9a" RelX="-0.8400000000001455" RelY="0.8900000000001" /> <Point X="3881.0" Y="1224.0" GraphRef="a9b07" RelX="0.0" RelY="0.9393939393939394" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349638" /> </Interaction> <Interaction GraphId="d6c3b"> <Comment Source="Reactome">Hepatic triacylglycerol lipase (LIPC, and lipoprotein lipase, LPL) are dimeric lipases (Hill et al. 1997) that hydrolyse triglycerides from circulating lipoproteins thereby playing important roles in lipoprotein remodeling and uptake. LIPC dimer (as well as LPL dimer) binds to an ER membrane protein known as lipase maturation factor 1 (LMF1) which can mediate secretion and enzymatic maturation of these lipases. Human LMF1 contain five TM segments that divide the protein into six separate domains with cytoplasmic and ER lumenal orientation thereby transporting LIPC dimer from ER lumen to the cytosol. The mechanism of LIPC dimer translocation from cytosol to secretion is unknown (Doolittle et al. 2009, Babilonia-Rosa &amp; Neher 2014). Another family member, LMF2, may function as LMF1 based on similarity. Defects in LMF1 can cause combined lipase deficiency (CLD; MIM:246650), characterised by hypertriglyceridemia caused by ER retention of both LIPC dimer and LPL dimer (Peterfy et al. 2007).</Comment> <BiopaxRef>e22</BiopaxRef> <BiopaxRef>eed</BiopaxRef> <BiopaxRef>b21</BiopaxRef> <BiopaxRef>a92</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="605.0" Y="389.0" /> <Point X="653.0" Y="418.0" /> <Anchor Position="0.0" Shape="None" GraphId="e4e73" /> <Anchor Position="0.99" Shape="None" GraphId="d2aa2" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785178" /> </Interaction> <Interaction GraphId="d6e3e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3640.0" Y="473.0" GraphRef="bbc42" RelX="0.03000000000020009" RelY="0.6000000000000227" /> <Point X="3641.0" Y="476.0" GraphRef="e97ed" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216756" /> </Interaction> <Interaction GraphId="d7ab1"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3253.0" Y="1326.0" GraphRef="a0b47" RelX="-0.017543859649122806" RelY="0.9130434782608695" /> <Point X="3253.0" Y="1330.0" GraphRef="d9163" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8854628" /> </Interaction> <Interaction GraphId="d7b27"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3656.0" Y="353.0" GraphRef="f84ea" RelX="0.7300000000000182" RelY="0.3199999999999932" /> <Point X="3763.0" Y="319.0" GraphRef="f5021" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216757" /> </Interaction> <Interaction GraphId="d8123"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1204.0" Y="523.0" GraphRef="f11cd" RelX="1.0" RelY="-0.043478260869565216" /> <Point X="1208.0" Y="579.0" GraphRef="decb1" RelX="-91.0" RelY="41.5" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174757" /> </Interaction> <Interaction GraphId="d82e9"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1646.0" Y="863.0" GraphRef="e556f" RelX="-0.2599999999999909" RelY="0.5099999999999909" /> <Point X="1643.0" Y="882.0" GraphRef="ab012" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174657" /> </Interaction> <Interaction GraphId="d836f"> <Comment Source="Reactome">Crebh(1-?) enters the nucleoplasm and induces the expression of APOA4, APOA5, APOC2, CIDEC and FGF21 (Lee et al. 2011). APOA4, APOA5 and APOC2 are known to augment lipoprotein lipase (LPL) activity. LPL is bound to the vascular endothelium, and hydrolyzes chylomicron and VLDL- associated TG to facilitate the transport of hydrolyzed fatty acids to peripheral cells. Patients with genetic defects in AOPC2, APOA5 or LPL display high circulating TG levels due to impaired TG clearance. Identification of APOA4, APOA5 and APOC2 as CREB-H target genes suggests that CREB-H might be involved in TG catabolism. CREB-H also strongly induces FGF21, a liver expressed hormone that has antidiabetic and TG- lowering effects, and CIDEC which encodes a lipid droplet-associated protein (Lee 2012).</Comment> <BiopaxRef>e90</BiopaxRef> <BiopaxRef>ad8</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="154.0" Y="164.0" /> <Point X="154.0" Y="297.0" /> <Anchor Position="0.0" Shape="None" GraphId="b23c5" /> <Anchor Position="0.99" Shape="None" GraphId="c647a" /> <Anchor Position="0.5" Shape="None" GraphId="f9298" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784622" /> </Interaction> <Interaction GraphId="d840e"> <Comment Source="Reactome">Extracellular apoA-I protein binds to the CUBN (cubilin) subunit of the CUBN:AMN complex associated with the plasma membrane. In the body, this complex is found on the apical surfaces of kidney glomerular cells, where it mediates binding and endocytosis of proteins in the glomerular filtrate, and on the apical surfaces of enterocytes, where it mediates uptake of several vitamins complexed with carrier proteins (notably vitamin B12 (cobalamin):intrinsic factor) (Kozyraki et al. 1999; Fyfe et al. 2004).</Comment> <BiopaxRef>b2c</BiopaxRef> <BiopaxRef>c3f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3623.0" Y="1272.0" /> <Point X="3623.0" Y="1341.0" /> <Anchor Position="0.0" Shape="None" GraphId="f0009" /> <Anchor Position="0.99" Shape="None" GraphId="b4f4f" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264848" /> </Interaction> <Interaction GraphId="d9226"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3540.0" Y="223.0" GraphRef="af996" RelX="-0.023255813953488372" RelY="1.0" /> <Point X="3584.0" Y="266.0" GraphRef="ecf74" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216723" /> </Interaction> <Interaction GraphId="d984f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3885.0" Y="537.0" GraphRef="e4364" RelX="1.0" RelY="0.0" /> <Point X="3879.0" Y="583.0" GraphRef="b78f6" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264695" /> </Interaction> <Interaction GraphId="d9d10"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1643.0" Y="463.0" GraphRef="df7d5" RelX="-1.0" RelY="0.0" /> <Point X="1628.0" Y="424.0" GraphRef="ded85" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174660" /> </Interaction> <Interaction GraphId="da024"> <Comment Source="Reactome">ATP-binding cassette sub-family A member 1 (ABCA1) is a key mediator of cholesterol and phospholipid efflux to apolipoprotein particles. This efflux activity is regulated by protein kinase A (PKA) site-specific phosphorylation of ABCA1 at Ser-1042 and Ser-2054, located in the nucleotide binding domains of ABCA1 (See et al. 2002).</Comment> <BiopaxRef>c1e</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3182.0" Y="319.0" /> <Point X="3269.0" Y="319.0" /> <Anchor Position="0.0" Shape="None" GraphId="bcb16" /> <Anchor Position="0.99" Shape="None" GraphId="daf26" /> <Anchor Position="0.5" Shape="None" GraphId="bd591" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682101" /> </Interaction> <Interaction GraphId="da607"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="808.0" Y="257.0" GraphRef="db459" RelX="0.7000000000000455" RelY="-0.7400000000000091" /> <Point X="709.0" Y="117.0" GraphRef="a53c6" RelX="0.0" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784676" /> </Interaction> <Interaction GraphId="da732"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1348.0" Y="639.0" GraphRef="ef8cb" RelX="0.9805825242718447" RelY="-0.02857142857142857" /> <Point X="1396.0" Y="635.0" GraphRef="ac3ca" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174690" /> </Interaction> <Interaction GraphId="da8cb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2977.0" Y="225.0" GraphRef="cbbc7" RelX="0.7899999999999636" RelY="0.009999999999990905" /> <Point X="2983.0" Y="271.0" GraphRef="b6d81" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682084" /> </Interaction> <Interaction GraphId="da95d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3788.0" Y="980.0" GraphRef="c2df2" RelX="0.9555555555555556" RelY="0.0" /> <Point X="3804.0" Y="937.0" GraphRef="cfc1d" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8980228" /> </Interaction> <Interaction GraphId="daad7"> <Comment Source="Reactome">LCAT activated by apoA-I catalyzes the reaction of cholesterol and phosphatidylcholine to yield cholesterol esterified with a long-chain fatty acid and 2-lysophosphatidylcholine. While this reaction was first studied in vitro using purified proteins in solution, it occurs in vivo on the surfaces of HDL particles where transiently-bound LCAT is activated by HDL-associated apoA-I protein and consumes HDL-associated cholesterol and phosphatidylcholine. The cholesterol ester reaction product is strongly associated with the HDL particle because of its increased hydrophobicity, while the 2-lysophosphatidylcholine product is released from the particle (Fielding et al. 1972 [2 references]; Adimoolam et al. 1998).</Comment> <BiopaxRef>f6a</BiopaxRef> <BiopaxRef>b20</BiopaxRef> <BiopaxRef>da3</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3879.0" Y="583.0" /> <Point X="3878.0" Y="656.0" /> <Anchor Position="0.0" Shape="None" GraphId="b78f6" /> <Anchor Position="0.99" Shape="None" GraphId="d9414" /> <Anchor Position="0.5" Shape="None" GraphId="bbe4e" /> <Anchor Position="0.5" Shape="None" GraphId="ded02" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264695" /> </Interaction> <Interaction GraphId="dab9a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3089.0" Y="678.0" GraphRef="f939f" RelX="0.0" RelY="1.0" /> <Point X="3088.0" Y="802.0" GraphRef="e197d" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349404" /> </Interaction> <Interaction GraphId="dad70"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3136.0" Y="655.0" GraphRef="f939f" RelX="1.0" RelY="0.0" /> <Point X="3250.0" Y="728.0" GraphRef="bc6d8" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266328" /> </Interaction> <Interaction GraphId="dafe3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3778.0" Y="334.0" GraphRef="f5021" RelX="0.0" RelY="1.0" /> <Point X="3779.0" Y="385.0" GraphRef="dd713" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349657" /> </Interaction> <Interaction GraphId="db6bc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2491.0" Y="1104.0" GraphRef="d1046" RelX="-1.0" RelY="0.0" /> <Point X="2488.0" Y="1104.0" GraphRef="ecffe" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876366" /> </Interaction> <Interaction GraphId="db822"> <Comment Source="Reactome">In macrophages, the hydrolysis of cholesteryl esters (CHESTs) is the rate-limiting step in the removal of free cholesterol (CHOL) from these cells. CHOL is transported via transport vesicles and can be used for cellular functions or removed from the cell by ABCA1 to create new HDL particles. Accumulation of CHESTs in macrophage foam cells is key to atherosclerotic plaque formation (Dubland &amp; Francis 2015). CHOL is positioned on the outer membrane of lysosomes and translocates to the ER membrane where it can be re-esterified for storage. The mechanism of translocation is currently unknown (Infante et al. 2008).</Comment> <BiopaxRef>e77</BiopaxRef> <BiopaxRef>b3e</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2152.0" Y="961.0" /> <Point X="2130.0" Y="907.0" /> <Anchor Position="0.0" Shape="None" GraphId="a899f" /> <Anchor Position="0.99" Shape="None" GraphId="cca0d" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876485" /> </Interaction> <Interaction GraphId="dbc9d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="563.0" Y="292.0" GraphRef="ca814" RelX="1.0" RelY="0.0" /> <Point X="606.0" Y="312.0" GraphRef="b58c4" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785181" /> </Interaction> <Interaction GraphId="dc6ac"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3081.0" Y="225.0" GraphRef="aa304" RelX="-0.008130081300813009" RelY="1.0" /> <Point X="3083.0" Y="228.0" GraphRef="f46c4" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682103" /> </Interaction> <Interaction GraphId="dc6bd"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1208.0" Y="636.0" GraphRef="f1f1d" RelX="-1.8199999999999363" RelY="1.9700000000000273" /> <Point X="1246.0" Y="639.0" GraphRef="ef8cb" RelX="-1.0" RelY="-0.02857142857142857" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174757" /> </Interaction> <Interaction GraphId="dcc23"> <Comment Source="Reactome">In macrophage foam cells, the hydrolysis of cholesteryl esters (CHESTs) is the rate-limiting step in the removal of free cholesterol (CHOL) from these cells. CHOL is transported via transport vesicles and can be used for cellular functions or removed from the cell by ABCA1 to create new HDL particles. Accumulation of CHESTs in macrophage foam cells is key to atherosclerotic plaque formation and occurs as a result of an imbalance between CHOL influx and efflux pathways. The main hydrolase that hydrolyses CE in macrophages is neutral cholesterol ester hydrolase 1 (NCEH1). Carboxylesterases (CESs), usually involved in the hydrolysis of drugs, can also hydrolyse CHESTs with CES1 responsible for &gt;70% of the total CES hydrolytic activity in macrophages, thus playing an important antiatherogenic role. CES1 knockdown studies reveal a compensatory increase in the expression of CES3, expressed at &lt;30% of the level of CES1 in human macrophages, which restores intracellular CHEST hydrolytic activity and CHOL efflux (Zhao et al. 2012). Human CES3 isoproteins are predicted to be either secreted or retained in the cytosol (Holmes et al. 2010) but the exact location is currently unknown.</Comment> <BiopaxRef>f51</BiopaxRef> <BiopaxRef>b8c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1923.0" Y="1151.0" /> <Point X="2045.0" Y="1152.0" /> <Anchor Position="0.0" Shape="None" GraphId="a8626" /> <Anchor Position="0.99" Shape="None" GraphId="f2ca2" /> <Anchor Position="0.5" Shape="None" GraphId="b6232" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8937442" /> </Interaction> <Interaction GraphId="dd190"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="918.0" Y="310.0" GraphRef="a9b01" RelX="-1.0" RelY="0.0" /> <Point X="808.0" Y="283.0" GraphRef="d750a" RelX="35.0" RelY="-11.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784676" /> </Interaction> <Interaction GraphId="dd590"> <Graphics ConnectorType="Segmented" 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</Interaction> <Interaction GraphId="de87f"> <Comment Source="Reactome">While the export pathway for nascent chylomicrons has not been directly characterized in human cells, the requirement for SAR1B protein for normal chylomicron export in vivo (Jones et al. 2003) indicates that nascent chylomicrons are exported from the endoplasmic reticulum via the Golgi apparatus in COPII vesicles.</Comment> <BiopaxRef>bdc</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1691.0" Y="135.0" /> <Point X="1690.0" Y="372.0" /> <Anchor Position="0.0" Shape="None" GraphId="d3bb7" /> <Anchor Position="0.99" Shape="None" GraphId="a950b" /> <Anchor Position="0.5" Shape="None" GraphId="da75b" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174587" /> </Interaction> <Interaction GraphId="de95e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3624.0" Y="853.0" GraphRef="ac82d" RelX="0.6900000000000546" RelY="1.0" /> <Point 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GraphRef="e2f45" RelX="0.0" RelY="0.3299999999999841" /> <Point X="606.0" Y="348.0" GraphRef="c441e" RelX="-0.013333333333333334" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785181" /> </Interaction> <Interaction GraphId="dfb11"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="815.0" Y="698.0" GraphRef="dd477" RelX="0.8300000000000409" RelY="0.0" /> <Point X="862.0" Y="698.0" GraphRef="f286b" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5694109" /> </Interaction> <Interaction GraphId="dff87"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2763.0" Y="621.0" GraphRef="e64c0" RelX="-1.0" RelY="-0.05263157894736842" /> <Point X="2685.0" Y="621.0" GraphRef="f0949" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-176879" /> </Interaction> <Interaction GraphId="e050c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3440.0" Y="627.0" GraphRef="e0311" RelX="0.6199999999998909" RelY="0.0" /> <Point X="3439.0" Y="579.0" GraphRef="fd144" RelX="-0.037037037037037035" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266082" /> </Interaction> <Interaction GraphId="e0ba9"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3438.0" Y="752.0" GraphRef="ca26c" RelX="-1.0" RelY="-0.030303030303030304" /> <Point X="3430.0" Y="809.0" GraphRef="f4dcc" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266303" /> </Interaction> <Interaction GraphId="e0bcf"> <Comment Source="Reactome">LPL enzyme is catalytically active as a dimer composed of two glycosylated subunits of LPL connected in a head-to-tail arrangement by non-covalent interactions. Dimeric LPL is cleaved by several proprotein convertases. Proprotein convertase subtilisin/kexin type 5 (PCSK5) can cleave LPL dimer, inactivating it, resulting in subsequent increase in plasma TG concentrations (Paule et al. 2012). ANGPTL4 binds transiently to LPL dimer, the interaction resulting in conversion of the enzyme from a catalytically active dimer to inactive, but still folded, monomers (Sukonina et al. 2006).</Comment> <BiopaxRef>f8d</BiopaxRef> <BiopaxRef>bdb</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="738.0" Y="331.0" /> <Point X="808.0" Y="257.0" /> <Anchor Position="0.0" Shape="None" GraphId="c49cd" /> <Anchor Position="0.99" Shape="None" GraphId="db459" /> <Anchor Position="0.5" Shape="None" GraphId="e5d48" /> <Anchor Position="0.5" Shape="None" GraphId="d750a" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784676" /> </Interaction> <Interaction GraphId="e0d0b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1529.0" Y="181.0" GraphRef="b7703" RelX="-0.0196078431372549" RelY="-1.0" /> <Point X="1541.0" Y="109.0" GraphRef="f2a75" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174741" /> </Interaction> <Interaction GraphId="e0e2c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3763.0" Y="319.0" GraphRef="f5021" RelX="-1.0" RelY="0.0" /> <Point X="3637.0" Y="413.0" GraphRef="bcb3d" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216756" /> </Interaction> <Interaction GraphId="e19c1"> <Comment Source="Reactome">The molecular details of this event are inferred from the dissociation of the LDL:LDLR complex in the endosome.</Comment> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1479.0" Y="1093.0" /> <Point X="1479.0" Y="1147.0" /> <Anchor Position="0.0" Shape="None" GraphId="a406e" /> <Anchor Position="0.99" Shape="None" GraphId="c1e2a" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174624" /> </Interaction> <Interaction GraphId="e1a36"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1952.0" Y="829.0" GraphRef="aa0a3" RelX="-0.6400000000001" RelY="0.009999999999990905" /> <Point X="1918.0" Y="829.0" GraphRef="f4548" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876696" /> </Interaction> <Interaction GraphId="e1b7f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3364.0" Y="392.0" GraphRef="b5ee4" RelX="0.0" RelY="-1.0" /> <Point X="3382.0" Y="365.0" GraphRef="eb655" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216727" /> </Interaction> <Interaction GraphId="e1bc5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="710.0" Y="197.0" GraphRef="a35c6" RelX="0.01999999999998181" RelY="0.46000000000000796" /> <Point X="711.0" Y="200.0" GraphRef="b6366" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784861" /> </Interaction> <Interaction GraphId="e1c28"> <Comment Source="Reactome">Lysosomal acid lipase/cholesteryl ester hydrolase (LIPA, aka lysosomal acid lipase, LAL) is structurally related to previously described enteric acid lipases and catalyses the deacylation of triacylglyceryl and cholesteryl ester core lipids of endocytosed low density lipoproteins (LDLs) (Anderson &amp; Sando 1991, Ameis et al. 1994). LIPA is catalytically active in monomeric form. Defects in LIPA can cause Wolman disease (WOD; MIM:278000), a lysosomal lipid storage disorder where cholesteryl esters and triglycerides accumulate in most tissues of the body. WOD occurs in infancy and is nearly always fatal before the age of 1 (Anderson et al. 1994, Du et al. 1998).&lt;br&gt;&lt;br&gt;Atherosclerosis is characterised by the accumulation of excess cholesterol in the artery wall. In later stages of atherosclerosis, both free cholesterol and cholesteryl ester droplets accumulate within the lysosome. As the cholesterol level increases, it inhibits the proton pumping ability of the vATPases, the pH inside the lysosome increases and renders LIPA catalytically inactive, contributing further to the progression of atherosclerosis (Dubland &amp; Francis 2015). </Comment> <BiopaxRef>d7c</BiopaxRef> <BiopaxRef>a4e</BiopaxRef> <BiopaxRef>f0c</BiopaxRef> <BiopaxRef>f03</BiopaxRef> <BiopaxRef>b3e</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2368.0" Y="1105.0" /> <Point X="2296.0" Y="1104.0" /> <Anchor Position="0.0" Shape="None" GraphId="cbfa3" /> <Anchor Position="0.99" Shape="None" GraphId="abe89" /> <Anchor Position="0.5" Shape="None" GraphId="a9b11" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8865667" /> </Interaction> <Interaction GraphId="e1d45"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3204.0" Y="370.0" GraphRef="e7e2b" RelX="-1.0" RelY="0.0" /> <Point X="3250.0" Y="414.0" GraphRef="b05a8" RelX="-14.0" RelY="0.5" ArrowHead="TBar" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264758" /> </Interaction> <Interaction GraphId="e2771"> <Comment Source="Reactome">Dimeric lipase G (LIPG) catalyzes the hydrolysis of triglycerides (TAG) associated with high-density lipoprotein particles to diglycerides (DAG) and long-chain fatty acids (LCFA) (Griffon et al. 2009).</Comment> <BiopaxRef>a9c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3804.0" Y="937.0" /> <Point X="3901.0" Y="937.0" /> <Anchor Position="0.0" Shape="None" GraphId="cfc1d" /> <Anchor Position="0.99" Shape="None" GraphId="a2738" /> <Anchor Position="0.5" Shape="None" GraphId="b5b07" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8980228" /> </Interaction> <Interaction GraphId="e2dd6"> <Comment Source="Reactome">Spherical HDL particles bound to the cell-surface SR-BI receptor are disassembled, with the release of pre-beta HDL (essentially apoA-I lipoprotein with a few molecules of bound lipid) and the cellular uptake of the bulk of the HDL-associated cholesterol, cholesterol esters, phospholipids, and triacylglycerols. The specificity and efficiency of this process has been demonstrated through a variety of studies in tissue culture model systems (Rigotti et al. 2003; Silver and Tall 2001). The process is annotated here as a concerted event occuring at the cell surface but its molecular details remain incompletely defined and it is possible that the HDL particle is internalized while undergoing disassembly.</Comment> <BiopaxRef>fea</BiopaxRef> <BiopaxRef>d68</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3882.0" Y="1391.0" /> <Point X="3798.0" Y="1480.0" /> <Anchor Position="0.0" Shape="None" GraphId="e1d16" /> <Anchor Position="0.99" Shape="None" GraphId="a5a9a" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349638" /> </Interaction> <Interaction GraphId="e3583"> <Comment Source="Reactome">Vigilin (HDL-binding protein, HDLBP) predominantly resides on most human cell membranes and binds high-density lipoproteins (HDLs). Although its role remains unclear, Vigilin may mediate removal of excess intracellular cholesterol (Bocharov et al. 2001).</Comment> <BiopaxRef>b83</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3808.0" Y="1153.0" /> <Point X="3741.0" Y="1153.0" /> <Anchor Position="0.0" Shape="None" GraphId="c82cc" /> <Anchor Position="0.99" Shape="None" GraphId="b4f2d" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8858252" /> </Interaction> <Interaction GraphId="e36c6"> <Comment Source="Reactome">ApoA-I bound to CUBN:AMN on the cell surface is endocytosed, moved to lysosomes, and degraded (Kozyraki et al. 1999). It is not known whether the CUBN:AMN complex is also degraded or recycled to the cell surface.</Comment> <BiopaxRef>b2c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3651.0" Y="1385.0" /> <Point X="3731.0" Y="1432.0" /> <Anchor Position="0.0" Shape="None" GraphId="e1f25" /> <Anchor Position="0.99" Shape="None" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264834" /> </Interaction> <Interaction GraphId="e425f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2277.0" Y="1318.0" GraphRef="f5baa" RelX="-0.6999999999998181" RelY="0.0" /> <Point X="2274.0" Y="1318.0" GraphRef="c40b0" RelX="1.0" RelY="-0.02702702702702703" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784738" /> </Interaction> <Interaction GraphId="e45bc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="711.0" Y="334.0" GraphRef="d846b" RelX="-0.010101010101010102" RelY="-1.0" /> <Point X="738.0" Y="331.0" GraphRef="c49cd" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784676" /> </Interaction> <Interaction GraphId="e4707"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3397.0" Y="413.0" GraphRef="b5ee4" RelX="1.0" RelY="0.0" /> <Point X="3637.0" Y="413.0" GraphRef="bcb3d" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216756" /> </Interaction> <Interaction GraphId="e475d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3624.0" Y="1382.0" GraphRef="c3f76" RelX="-0.010101010101010102" RelY="1.0" /> <Point X="3651.0" Y="1385.0" GraphRef="e1f25" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264834" /> </Interaction> <Interaction GraphId="e479f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3798.0" Y="1480.0" GraphRef="a5a9a" RelX="-0.8400000000001455" RelY="0.8900000000001" /> <Point X="3926.0" Y="1534.0" GraphRef="d0496" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349638" /> </Interaction> <Interaction GraphId="e4b3a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3269.0" Y="319.0" GraphRef="daf26" RelX="0.8699999999998909" RelY="0.0" /> <Point X="3298.0" Y="319.0" GraphRef="b6a22" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682101" /> </Interaction> <Interaction GraphId="e53aa"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="204.0" Y="209.0" GraphRef="aa465" RelX="-1.0" RelY="-0.030303030303030304" /> <Point X="154.0" Y="211.0" GraphRef="f9298" RelX="0.0" RelY="-19.5" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784622" /> </Interaction> <Interaction GraphId="e6798"> <Comment Source="Reactome">Once low-density lipoprotein (LDL) is freed from the LDLR to the endosomal lumen, it translocates to the lysosomal lumen for degradation via a receptor-mediated endocytotic mechanism (Goldstein et al. 1979).</Comment> <BiopaxRef>a59</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2488.0" Y="1104.0" /> <Point X="2424.0" Y="1105.0" /> <Anchor Position="0.0" Shape="None" GraphId="ecffe" /> <Anchor Position="0.99" Shape="None" GraphId="c6daf" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876366" /> </Interaction> <Interaction GraphId="e6cca"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="772.0" Y="618.0" GraphRef="b9040" RelX="0.009999999999990905" RelY="0.6900000000000546" /> <Point X="773.0" Y="621.0" GraphRef="fe92f" RelX="-0.012048192771084338" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785213" /> </Interaction> <Interaction GraphId="e74e0"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2390.0" Y="1053.0" GraphRef="b21bb" RelX="-0.023255813953488372" RelY="1.0" /> <Point X="2368.0" Y="1105.0" GraphRef="cbfa3" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8865667" /> </Interaction> <Interaction GraphId="e7734"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3269.0" Y="319.0" GraphRef="daf26" RelX="0.8699999999998909" RelY="0.0" /> <Point X="3299.0" Y="273.0" GraphRef="ac29a" RelX="-0.024390243902439025" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682101" /> </Interaction> <Interaction GraphId="e7843"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2679.0" Y="1009.0" GraphRef="b47db" RelX="0.9555555555555556" RelY="0.0" /> <Point X="2783.0" Y="930.0" GraphRef="aaf3b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171122" /> </Interaction> <Interaction GraphId="e7a61"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2535.0" Y="980.0" GraphRef="a974d" RelX="-0.3000000000001819" RelY="0.5599999999999454" /> <Point X="2535.0" Y="983.0" GraphRef="f6715" RelX="-0.012658227848101266" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171059" /> </Interaction> <Interaction GraphId="e7c73"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="815.0" Y="698.0" GraphRef="dd477" RelX="0.8300000000000409" RelY="0.0" /> <Point X="846.0" Y="720.0" GraphRef="fc3d3" RelX="-0.02702702702702703" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5694109" /> </Interaction> <Interaction GraphId="e7d25"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2849.0" Y="207.0" GraphRef="af7c7" RelX="1.0" RelY="0.0" /> <Point X="2898.0" Y="224.0" GraphRef="f0fd2" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682084" /> </Interaction> <Interaction GraphId="e888b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3798.0" Y="1480.0" GraphRef="a5a9a" RelX="-0.8400000000001455" RelY="0.8900000000001" /> <Point X="3846.0" Y="1585.0" GraphRef="c4543" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349638" /> </Interaction> <Interaction GraphId="e8e3a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2994.0" Y="619.0" GraphRef="a06b9" RelX="0.6999999999998181" RelY="0.0" /> <Point X="3042.0" Y="655.0" GraphRef="f939f" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266350" /> </Interaction> <Interaction GraphId="e95dc"> <Comment Source="Reactome">Newly formed very low-density lipoprotein (VLDL) released from the liver can acquire lipoproteins in the circulation. Apolipoprotein C-I (APOC1) is a 6.6 kDa apolipoprotein that is synthesised mainly in the liver but also in other tissues. It is a constituent of triglyceride-rich lipoproteins (around 10% of the protein of VLDLs and 2% of HDLs) that slow the circulatory clearance of triglyceride-rich lipoproteins by a variety of mechanisms. As well as binding and inhibiting triglyceride-rich lipoprotein uptake by the very low-density lipoprotein receptor (VLDLR), it can also binds free fatty acids (FAs) in the circulation, reducing their uptake by cells (Shachter 2001, Hansen et al. 2011). A minor constituent of VLDL is apolipoprotein IV (APO4) (Kotite et al. 2003).</Comment> <BiopaxRef>bb1</BiopaxRef> <BiopaxRef>ddf</BiopaxRef> <BiopaxRef>d27</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2440.0" Y="436.0" /> <Point X="2309.0" Y="436.0" /> <Anchor Position="0.0" Shape="None" GraphId="caa5a" /> <Anchor Position="0.99" Shape="None" GraphId="ee849" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866321" /> </Interaction> <Interaction GraphId="e965b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="920.0" Y="105.0" GraphRef="e172b" RelX="1.0" RelY="0.0" /> <Point X="929.0" Y="141.0" GraphRef="a4c9b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8856525" /> </Interaction> <Interaction GraphId="e99aa"> <Comment Source="Reactome">In macrophages, the hydrolysis of cholesteryl esters (CHESTs) is the rate-limiting step in the removal of free cholesterol (CHOL) from these cells. CHOL is transported via transport vesicles and can be used for cellular functions or removed from the cell by ABCA1 to create new HDL particles. Accumulation of CHESTs in macrophage foam cells is key to atherosclerotic plaque formation (Dubland &amp; Francis 2015). Exit from lysosomes of CHOL derived from the hydrolysis of CHESTs in low-density lipoproteins (LDLs) requires the concerted effort of two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. In the first step, NPC2 binds unesterified CHOL that has been released from LDLs in the lumen of lysosomes (Liou et al. 2006).</Comment> <BiopaxRef>fb3</BiopaxRef> <BiopaxRef>b3e</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2333.0" Y="975.0" /> <Point X="2332.0" Y="909.0" /> <Anchor Position="0.0" Shape="None" GraphId="b4a0a" /> <Anchor Position="0.99" Shape="None" GraphId="b9a87" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876472" /> </Interaction> <Interaction GraphId="ea0d6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2218.0" Y="65.0" GraphRef="ddda8" RelX="0.9692307692307692" RelY="0.0" /> <Point X="2208.0" Y="79.0" GraphRef="aacf5" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866308" /> </Interaction> <Interaction GraphId="ea6be"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1727.0" Y="195.0" GraphRef="f9a3b" RelX="-1.0" RelY="0.0" /> <Point X="1691.0" Y="195.0" GraphRef="da75b" RelX="0.5" RelY="-58.5" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174587" /> </Interaction> <Interaction GraphId="ea7cb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2686.0" Y="586.0" GraphRef="f0c63" RelX="0.0" RelY="1.0" /> <Point X="2685.0" Y="621.0" GraphRef="f0949" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-176879" /> </Interaction> <Interaction GraphId="eaa60"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3143.0" Y="319.0" GraphRef="f1a2e" RelX="0.983739837398374" RelY="0.0" /> <Point X="3182.0" Y="319.0" GraphRef="bcb16" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682101" /> </Interaction> <Interaction GraphId="eab86"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2509.0" Y="535.0" GraphRef="d02af" RelX="0.599999999999909" RelY="-0.009999999999990905" /> <Point X="2512.0" Y="537.0" GraphRef="fe382" RelX="-1.0" RelY="-0.02702702702702703" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8933292" /> </Interaction> <Interaction GraphId="eabfc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3550.0" Y="920.0" GraphRef="d632a" RelX="0.010000000000218279" RelY="0.7400000000000091" /> <Point X="3551.0" Y="923.0" GraphRef="aa88d" RelX="-0.01098901098901099" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266315" /> </Interaction> <Interaction GraphId="eb184"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1317.0" Y="245.0" GraphRef="a51f6" RelX="0.0" RelY="-1.0" /> <Point X="1317.0" Y="116.0" GraphRef="d9718" RelX="-16.0" RelY="18.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174786" /> </Interaction> <Interaction GraphId="eb47d"> <Comment Source="Reactome">The six aminoterminal residues of pro-apolipoprotein A-1 are removed to generate the mature, lipid-binding form of the protein (APOA1). Studies of tissue culture systems suggest that BMP1 catalyzes this reaction (Chau et al. 2006, 2007). While BMP1 is annotated here as a monomer, its subunit structure is not known, and its 1:1 association with Zn2+ is inferred from its sequence similarity to known metallopeptidases. Tetrameric alpha2-macroglobulin (A2M) at concentrations found in plasma in inflammatory responses inhibits this reaction in vitro, suggesting a possible link between inflammation and perturbation of HDL function (Zhang et al. 2006, Chau et al. 2007).</Comment> <BiopaxRef>c37</BiopaxRef> <BiopaxRef>a41</BiopaxRef> <BiopaxRef>c29</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3200.0" Y="414.0" /> <Point X="3328.0" Y="413.0" /> <Anchor Position="0.0" Shape="None" GraphId="b5668" /> <Anchor Position="0.99" Shape="None" GraphId="bec1e" /> <Anchor Position="0.5" Shape="None" GraphId="df240" /> <Anchor Position="0.5" Shape="None" GraphId="b05a8" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264758" /> </Interaction> <Interaction GraphId="eb80a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2391.0" Y="1106.0" GraphRef="aa0a7" RelX="-1.0" RelY="0.0" /> <Point X="2368.0" Y="1105.0" GraphRef="cbfa3" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8865667" /> </Interaction> <Interaction GraphId="eb913"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1490.0" Y="109.0" GraphRef="f9f3d" RelX="0.9805825242718447" RelY="0.0" /> <Point X="1541.0" Y="109.0" GraphRef="f2a75" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174741" /> </Interaction> <Interaction GraphId="eb98a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1944.0" Y="1131.0" GraphRef="cc9d9" RelX="0.0" RelY="1.0" /> <Point X="1923.0" Y="1151.0" GraphRef="a8626" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8937442" /> </Interaction> <Interaction GraphId="ebadc"> <Comment Source="Reactome">Newly formed very low-density lipoprotein (VLDL) is released from the liver to the circulation (Tiwari &amp; Siddiqi 2012).</Comment> <BiopaxRef>cbd</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2526.0" Y="123.0" /> <Point X="2526.0" Y="413.0" /> <Anchor Position="0.0" Shape="None" GraphId="f43ee" /> <Anchor Position="0.99" Shape="None" GraphId="d9a6d" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866327" /> </Interaction> <Interaction GraphId="ebb13"> <Comment Source="Reactome">LCAT (lecithin-cholesterol acyltransferase) associates strongly but reversibly with spherical HDL particles (Jonas 2000).</Comment> <BiopaxRef>da3</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3549.0" Y="846.0" /> <Point X="3550.0" Y="920.0" /> <Anchor Position="0.0" Shape="None" GraphId="c30d5" /> <Anchor Position="0.99" Shape="None" GraphId="d632a" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266315" /> </Interaction> <Interaction GraphId="ebdac"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="653.0" Y="418.0" GraphRef="d2aa2" RelX="0.4800000000000182" RelY="0.29000000000002046" /> <Point X="746.0" Y="499.0" GraphRef="ef242" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785178" /> </Interaction> <Interaction GraphId="ec027"> <Comment Source="Reactome">Torcetrapib associates with a molecule of CETP and a spherical HDL particle to form a stable complex, thus trapping CETP and inhibiting CETP-mediated lipid transfer between HDL and LDL (Clark et al. 2006).</Comment> <BiopaxRef>b30</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3088.0" Y="802.0" /> <Point X="3088.0" Y="874.0" /> <Anchor Position="0.0" Shape="None" GraphId="e197d" /> <Anchor Position="0.99" Shape="None" GraphId="d126d" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-349404" /> </Interaction> <Interaction GraphId="ec5f8"> <Comment Source="Reactome">Palmitoylation of ATP-binding cassette sub-family A member 1 (ABCA1) at Cys 3, 23, 1110 and 1111 is essential for its proper trafficking from the ER membrane to the plasma membrane where it is essential for the transport of lipids (Singaraja et al. 2009).</Comment> <BiopaxRef>b85</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3083.0" Y="228.0" /> <Point X="3084.0" Y="298.0" /> <Anchor Position="0.0" Shape="None" GraphId="f46c4" /> <Anchor Position="0.99" Shape="None" GraphId="e1b46" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682103" /> </Interaction> <Interaction GraphId="ece67"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2388.0" Y="184.0" GraphRef="a9775" RelX="1.0" RelY="0.0" /> <Point X="2458.0" Y="144.0" GraphRef="e5ebb" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866304" /> </Interaction> <Interaction GraphId="ed31e"> <Comment Source="Reactome">The assembly of very low-density lipoprotein (VLDL) occurs in two steps (Olofsson et al. 2000). In the first step, apolipoprotein B-100 (APOB(28-4563), APOB-100) is co- and post-translationally lipidated by MTP (microsomal triacylglycerol transfer protein) in the form of a MTP:PDI (protein disulfide isomerase) heterodimer (Gordon et al. 1995), forming a pre-VLDL. This occurs in the rough endoplasmic reticulum (RER) lumen. The pre-VLDL is loosely associated with the RER membrane. MTP in vitro binds small amounts of PL and TAG (annotated here as one molecule of each) and efficiently transfers the bound lipid between membranes (Atzel &amp; Wetterau 1994). In vivo, MTP:PDI directly interacts with APOB-100 polypeptide (Wu et al. 1996), and is thought to transfer lipid from the endoplasmic reticulum membrane to nascent APOB-100. In humans, APOB-100 is expressed in the liver and forms VLDL whereas APOB-48 is expressed in the intestine and forms chylomicrons.</Comment> <BiopaxRef>dc2</BiopaxRef> <BiopaxRef>bf6</BiopaxRef> <BiopaxRef>ef9</BiopaxRef> <BiopaxRef>ef6</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2067.0" Y="120.0" /> <Point X="2170.0" Y="79.0" /> <Anchor Position="0.0" Shape="None" GraphId="f5c9b" /> <Anchor Position="0.99" Shape="None" GraphId="b3836" /> <Anchor Position="0.5" Shape="None" GraphId="bd4a8" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866329" /> </Interaction> <Interaction GraphId="ed5a8"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2477.0" Y="183.0" GraphRef="f4c77" RelX="-0.01818181818181818" RelY="-1.0" /> <Point X="2458.0" Y="144.0" GraphRef="e5ebb" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866304" /> </Interaction> <Interaction GraphId="ed73f"> <Comment Source="Reactome">Extracellular apolipoprotein A-I interacts with phospholipid- and cholesterol-rich membrane patches formed through the action of ABCA1, binding these two lipids to form a discoidal (small nascent) HDL particle (HDL 3c - Kontush and Chapman 2006). The apoA-I molecules that accept lipids in this reaction appear to be different from the ones that activate ABCA1 at the plasma membrane (Hassan et al. 2007; Vedhachalam et al. 2007).</Comment> <BiopaxRef>d8c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3637.0" Y="413.0" /> <Point X="3640.0" Y="473.0" /> <Anchor Position="0.0" Shape="None" GraphId="bcb3d" /> <Anchor Position="0.99" Shape="None" GraphId="bbc42" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216756" /> </Interaction> <Interaction GraphId="edfc2"> <Comment Source="Reactome">CETP (cholesterol ester transfer protein) complexed with cholesterol esters interacts with an LDL (low density lipoprotein) particle, acquiring triacylglycerol molecules and donating cholesterol ester to the LDL (Swenson et al. 1988; Morton and Zilversmit 1983). This process is reversible but in the body proceeds in the direction annotated here. A model for the lipid exchange process has been proposed based on recent studies of the structure of CETP:lipid complexes (Qiu et al. 2007).&lt;br&gt;&lt;br&gt;Apolipoprotein F (APOF) can be associated with HDLs and LDLs. It can inhibit cholesteryl ester transfer protein (CETP) activity, thus inhibiting CETP-mediated transfer events specifically involving the LDL particle (Wang et al. 1999). The function of HDL-associated APOF, which represents &gt;75% of the total plasma pool, is currently unknown. Although over-expression of mouse ApoF can accelerate plasma clearance of HDL (Lagor et al. 2009), physiological levels of ApoF do not affect HDL clearance (Lagor et al. 2012).&lt;br&gt;&lt;br&gt;Apolipoprotein C-I (APOC1) is an Inhibitor of lipoproteins binding to their respective low density lipoprotein LDL receptor (LDLR), LDL receptor-related protein, and very low density lipoprotein receptor (VLDLR). It directly binds circulating fatty acids therby inhibiting their cellular uptake and is also the major plasma inhibitor of CETP (Westerterp et al. 2007).</Comment> <BiopaxRef>cc5</BiopaxRef> <BiopaxRef>fab</BiopaxRef> <BiopaxRef>d7a</BiopaxRef> <BiopaxRef>d74</BiopaxRef> <BiopaxRef>c15</BiopaxRef> <BiopaxRef>eb1</BiopaxRef> <BiopaxRef>c7a</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2924.0" Y="619.0" /> <Point X="2994.0" Y="619.0" /> <Anchor Position="0.0" Shape="None" GraphId="c87ec" /> <Anchor Position="0.99" Shape="None" GraphId="a06b9" /> <Anchor Position="0.5" Shape="None" GraphId="a48df" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266350" /> </Interaction> <Interaction GraphId="ee1b8"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="606.0" Y="386.0" GraphRef="c441e" RelX="-0.013333333333333334" RelY="1.0" /> <Point X="605.0" Y="389.0" GraphRef="e4e73" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785178" /> </Interaction> <Interaction GraphId="eeace"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3455.0" Y="347.0" GraphRef="e887c" RelX="0.7300000000000182" RelY="-0.18000000000000682" /> <Point X="3440.0" Y="318.0" GraphRef="afb36" RelX="-1.0" RelY="-0.0196078431372549" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216727" /> </Interaction> <Interaction GraphId="eeaf0"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1577.0" Y="681.0" GraphRef="d66b2" RelX="1.0" RelY="0.0" /> <Point X="1601.0" Y="680.0" GraphRef="b5921" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174739" /> </Interaction> <Interaction GraphId="ef0c5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3943.0" Y="692.0" GraphRef="ef62a" RelX="0.0" RelY="1.0" /> <Point X="3943.0" Y="748.0" GraphRef="e888c" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264679" /> </Interaction> <Interaction GraphId="ef382"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="808.0" Y="257.0" GraphRef="db459" RelX="0.7000000000000455" RelY="-0.7400000000000091" /> <Point X="743.0" Y="275.0" GraphRef="de1dd" RelX="0.9692307692307692" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784676" /> </Interaction> <Interaction GraphId="ef9af"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1691.0" Y="131.0" GraphRef="d2bdc" RelX="0.0" RelY="0.9487179487179487" /> <Point X="1691.0" Y="135.0" GraphRef="d3bb7" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174587" /> </Interaction> <Interaction GraphId="f0bbc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3408.0" Y="842.0" GraphRef="a3b9f" RelX="0.9636363636363636" RelY="-0.043478260869565216" /> <Point X="3430.0" Y="809.0" GraphRef="f4dcc" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266303" /> </Interaction> <Interaction GraphId="f16e6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="709.0" Y="117.0" GraphRef="a53c6" RelX="0.0" RelY="1.0" /> <Point X="708.0" Y="151.0" GraphRef="d8900" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784861" /> </Interaction> <Interaction GraphId="f177c"> <Comment Source="Reactome">Once proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to very low-density lipoprotein receptor (VLDLR), the resultant complex is internalised via the canonical clathrin-dependent endocytic machinery. This degradation route that does not require ubiquitination of the cytoplasmic tail of the receptor and does not involve proteasomal or autophagy pahtways (Zhang et al. 2007, Poirier et al. 2008).</Comment> <BiopaxRef>b1c</BiopaxRef> <BiopaxRef>f65</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3159.0" Y="1164.0" /> <Point X="3094.0" Y="1163.0" /> <Anchor Position="0.0" Shape="None" GraphId="c360e" /> <Anchor Position="0.99" Shape="None" GraphId="b5f71" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8855131" /> </Interaction> <Interaction GraphId="f19bd"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2786.0" Y="630.0" GraphRef="e64c0" RelX="0.0" RelY="0.8947368421052632" /> <Point X="2783.0" Y="930.0" GraphRef="aaf3b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171122" /> </Interaction> <Interaction GraphId="f1a17"> <Comment Source="Reactome">Cholesterol that has been esterified by sterol O-acyltransferases at the ER membrane to cholesteryl esters (CHESTs) are stored in lipid particles present in the cytosol (Daugherty et al. 2008).</Comment> <BiopaxRef>d9f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1894.0" Y="898.0" /> <Point X="1879.0" Y="1044.0" /> <Anchor Position="0.0" Shape="None" GraphId="b8a4f" /> <Anchor Position="0.99" Shape="None" GraphId="d07f3" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876731" /> </Interaction> <Interaction GraphId="f1b34"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2246.0" Y="959.0" GraphRef="e4a66" RelX="0.0" RelY="0.6100000000000136" /> <Point X="2254.0" Y="995.0" GraphRef="c9d5f" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876484" /> </Interaction> <Interaction GraphId="f1b4f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3762.0" 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The binding site of PCSK9 has been localized to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR (Zhang et al. 2007). The complex PCSK9:LDLR is internalized via clathrin-mediated endocytosis and then routed to lysosomes via a mechanism that does not require ubiquitination and is distinct from the autophagy and proteosomal degradation pathways. In lysosomes, the affinity of the interaction between PCSK9 and LDLR dramatically increases. This promotes the final degradation of PCSK9 and LDLR without recycling. Monoclonal antibodies targeting PCSK9 have been shown to markedly reduce LDL cholesterol levels and are a novel treatment strategy for adults with hypercholesterolemia (Navarese et al. 2015).</Comment> <BiopaxRef>f65</BiopaxRef> <BiopaxRef>f87</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2657.0" Y="1056.0" /> <Point X="2656.0" Y="1151.0" /> <Anchor Position="0.0" Shape="None" GraphId="e1b9e" /> <Anchor Position="0.99" Shape="None" GraphId="f6fe5" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6784734" /> </Interaction> <Interaction GraphId="f508b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="760.0" Y="354.0" GraphRef="d846b" RelX="0.9797979797979798" RelY="0.0" /> <Point X="1208.0" Y="579.0" GraphRef="bdf13" RelX="-91.0" RelY="41.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174757" /> </Interaction> <Interaction GraphId="f56da"> <Comment Source="Reactome">In the body, this binding involved apoE synthesized by hepatocytes and concentrated in the space of Disse, an extracellular compartment adjacent to the hepatocytes to which blood-borne lipoprotein particles have free access (Ji et al. 1994).</Comment> <BiopaxRef>d42</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1601.0" Y="680.0" /> <Point X="1676.0" Y="681.0" /> <Anchor Position="0.0" Shape="None" GraphId="b5921" /> <Anchor Position="0.99" Shape="None" GraphId="bafdc" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174739" /> </Interaction> <Interaction GraphId="f5c68"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3586.0" Y="1251.0" GraphRef="fc97b" RelX="1.0" RelY="0.0" /> <Point X="3623.0" Y="1272.0" GraphRef="f0009" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264848" /> </Interaction> <Interaction GraphId="f5daf"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3641.0" Y="498.0" GraphRef="e97ed" RelX="0.0" RelY="1.0" /> <Point X="3638.0" Y="643.0" GraphRef="e23fb" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266089" /> </Interaction> <Interaction GraphId="f635e"> <Comment Source="Reactome">Once proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to very low-density lipoprotein receptor (VLDLR), the resultant complex is internalised via the canonical clathrin-dependent endocytic machinery. This degradation route that does not require ubiquitination of the cytoplasmic tail of the receptor and does not involve proteasomal or autophagy pathways. The PCSK9:VLDLR:Clathrin-coated vesicle complex translocates from the plasma membrane, via endosomes to the lysosomal membrane where the receptor is degraded (Zhang et al. 2007, Poirier et al. 2008).</Comment> <BiopaxRef>f65</BiopaxRef> <BiopaxRef>b1c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3051.0" Y="1190.0" /> <Point X="3053.0" Y="1245.0" /> <Anchor Position="0.0" Shape="None" GraphId="c5458" /> <Anchor Position="0.99" Shape="None" GraphId="d7583" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8855130" /> </Interaction> <Interaction GraphId="f6c20"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2130.0" Y="907.0" GraphRef="cca0d" RelX="-0.2199999999997999" RelY="-0.5399999999999636" /> <Point X="2151.0" Y="876.0" GraphRef="c04f6" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876485" /> </Interaction> <Interaction GraphId="f75ba"> <Comment Source="Reactome">Fatty acids (FAs) are used as energy substrates and are stored as triglycerides. Triacylglycerol (TAG) has to be cleaved by lipases to be able to move in and out of cells for usage. Hepatic triacylglycerol lipase (LIPC) is one of several enzymes that catalyses the hydrolysis of TAGs to free fatty acids (FAs) and diacylglycerol (DAG) (Hegele et al. 1993, Santamarina-Fojo et al. 2004). Defects in LIPC can cause hepatic lipase deficiency (HL deficiency; MIM:614025), a disorder characterised by premature atherosclerosis and abnormal circulating lipoproteins (Hegele et al. 1992, 1993).</Comment> <BiopaxRef>e63</BiopaxRef> <BiopaxRef>e7a</BiopaxRef> <BiopaxRef>f88</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="732.0" Y="698.0" /> <Point X="815.0" Y="698.0" /> <Anchor Position="0.0" Shape="None" GraphId="b12e0" /> <Anchor Position="0.99" Shape="None" GraphId="dd477" /> <Anchor Position="0.5" Shape="None" GraphId="dcf13" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5694109" /> </Interaction> <Interaction GraphId="f76a6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2957.0" Y="571.0" GraphRef="ece25" RelX="-0.017543859649122806" RelY="0.9130434782608695" /> <Point X="2957.0" Y="619.0" GraphRef="a48df" RelX="-2.0" RelY="0.0" ArrowHead="TBar" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266350" /> </Interaction> <Interaction GraphId="f772a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2313.0" Y="109.0" GraphRef="c66f7" RelX="1.050000000000182" RelY="0.29999999999999716" /> <Point X="2316.0" Y="109.0" GraphRef="f3b98" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866308" /> </Interaction> <Interaction GraphId="f7aa6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3143.0" Y="273.0" GraphRef="d9dd4" RelX="0.0" RelY="1.0" /> <Point X="3182.0" Y="319.0" GraphRef="bcb16" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5682101" /> </Interaction> <Interaction GraphId="f7c47"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3503.0" Y="705.0" GraphRef="c15ea" RelX="0.0" RelY="1.0" /> <Point X="3555.0" Y="753.0" GraphRef="aa5b5" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266299" /> </Interaction> <Interaction GraphId="f7ea9"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1952.0" Y="829.0" GraphRef="aa0a3" RelX="-0.6400000000001" RelY="0.009999999999990905" /> <Point X="1932.0" Y="880.0" GraphRef="a3e90" RelX="0.9649122807017544" RelY="-0.034482758620689655" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876696" /> </Interaction> <Interaction GraphId="f802a"> <Comment Source="Reactome">ABCA1 associated with the plasma membrane binds extracellular apolipoprotein A-I (APOA1), forming a membrane-associated complex. The predominant form of ABCA1 is a heterotetramer (Denis et al. 2004), although studies in model systems in vitro are consistent with the hypothesis that the protein may also occur as a dimer (Trompier et al. 2006).</Comment> <BiopaxRef>cd1</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3382.0" Y="365.0" /> <Point X="3455.0" Y="347.0" /> <Anchor Position="0.0" Shape="None" GraphId="eb655" /> <Anchor Position="0.99" Shape="None" GraphId="e887c" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-216727" /> </Interaction> <Interaction GraphId="f8635"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2002.0" Y="1063.0" GraphRef="c8b67" RelX="0.38000000000010914" RelY="0.009999999999990905" /> <Point X="2054.0" Y="1062.0" GraphRef="ba624" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6813720" /> </Interaction> <Interaction GraphId="f868f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2108.0" Y="217.0" GraphRef="de690" RelX="0.0" RelY="-1.0" /> <Point X="2109.0" Y="120.0" GraphRef="bd4a8" RelX="-9.5" RelY="20.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866329" /> </Interaction> <Interaction GraphId="f8c8d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3551.0" Y="923.0" GraphRef="aa88d" RelX="-0.01098901098901099" RelY="-1.0" /> <Point X="3558.0" Y="920.0" GraphRef="ed4e8" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266310" /> </Interaction> <Interaction GraphId="f8d08"> <Comment Source="Reactome">Low density lipoprotein (LDL) particles bound to their receptors (LDLR) in coated pits on the cell surface are taken up into clathrin-coated vesicles (Goldstein et al. 1979). In hepatocytes and lymphocytes, but not in fibroblasts, this process requires the presence of an additional protein, LDLRAP1 (ARH1). In human patients, LDLRAP1 deficiency is associated with hypercholesterolemia, emphasizing the central role of the liver in clearance of circulating LDL in vivo (Eden et al. 2002; Garuti et al. 2005; He et al. 2002; Michaely et al. 2004). In vitro, LDLRAP1 protein binds both to LDLR and to components of the clathrin coat, suggesting that it might play an essential bridging function during the movement of LDL:LDLR complexes into clathrin-coated vesicles. This role has not yet been demonstrated in vivo, however, nor is it clear what might substitute for such a bridging function in fibroblasts.</Comment> <BiopaxRef>a59</BiopaxRef> <BiopaxRef>ebb</BiopaxRef> <BiopaxRef>ff6</BiopaxRef> <BiopaxRef>bd2</BiopaxRef> <BiopaxRef>ab3</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2657.0" Y="845.0" /> <Point X="2628.0" Y="901.0" /> <Anchor Position="0.0" Shape="None" GraphId="d14ea" /> <Anchor Position="0.99" Shape="None" GraphId="e3bd8" /> <Anchor Position="0.5" Shape="None" GraphId="e4ec3" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-171141" /> </Interaction> <Interaction GraphId="f917e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2171.0" Y="964.0" GraphRef="a4a47" RelX="-0.017543859649122806" RelY="-1.0" /> <Point X="2152.0" Y="961.0" GraphRef="a899f" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876485" /> </Interaction> <Interaction GraphId="f96dd"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3051.0" Y="1187.0" GraphRef="e302a" RelX="-0.012658227848101266" RelY="1.0" /> <Point X="3051.0" Y="1190.0" GraphRef="c5458" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8855130" /> </Interaction> <Interaction GraphId="fa09d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3413.0" Y="680.0" GraphRef="cf8db" RelX="0.0" RelY="-1.0" /> <Point X="3413.0" Y="626.0" GraphRef="ac919" RelX="4.0" RelY="-1.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266082" /> </Interaction> <Interaction GraphId="fa0aa"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1981.0" Y="982.0" GraphRef="d35d7" RelX="0.0" RelY="1.0" /> <Point X="1983.0" Y="1062.0" GraphRef="a54d9" RelX="0.0" RelY="-0.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6813720" /> </Interaction> <Interaction GraphId="fa203"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2130.0" Y="907.0" GraphRef="cca0d" RelX="-0.2199999999997999" RelY="-0.5399999999999636" /> <Point X="2091.0" Y="879.0" GraphRef="b88da" RelX="0.9607843137254902" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8876485" /> </Interaction> <Interaction GraphId="fa396"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2380.0" Y="147.0" GraphRef="aa1d8" RelX="1.0" RelY="0.0" /> <Point X="2458.0" Y="144.0" GraphRef="e5ebb" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8866304" /> </Interaction> <Interaction GraphId="fac1f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3819.0" Y="983.0" GraphRef="fe940" RelX="-1.0" RelY="0.0" /> <Point X="3856.0" Y="937.0" GraphRef="b5b07" RelX="3.5" RelY="0.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8980228" /> </Interaction> <Interaction GraphId="fb00c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1566.0" Y="220.0" GraphRef="a5814" RelX="-0.0196078431372549" RelY="-1.0" /> <Point X="1541.0" Y="109.0" GraphRef="f2a75" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174741" /> </Interaction> <Interaction GraphId="fb28f"> <Comment Source="Reactome">Spherical (mature) HDL particles can acquire additional molecules of free cholesterol (CHOL) and phospholipid (PL) from cell membranes. In the body, this is an important step in the so-called reverse cholesterol transport process in which excess CHOLl, notably in foam cells in atherosclerotic plaques, is transferred to HDL particles and transported ultimately to the liver. While studies in vitro and in mutant mice indicate that PLTP (phospholipid transfer protein) plays a major role in this process, its molecular details remain unclear (Oram et al. 2003) and the reaction is annotated here as the addition of two molecules each of CHOL and PL to a spherical HDL to create an "enlarged" spherical HDL.</Comment> <BiopaxRef>fd7</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3555.0" Y="753.0" /> <Point X="3624.0" Y="853.0" /> <Anchor Position="0.0" Shape="None" GraphId="aa5b5" /> <Anchor Position="0.99" Shape="None" GraphId="ac82d" /> <Anchor Position="0.5" Shape="None" GraphId="a7e8e" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266299" /> </Interaction> <Interaction GraphId="fc1b2"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3766.0" Y="938.0" GraphRef="aaa43" RelX="1.0" RelY="0.0" /> <Point X="3804.0" Y="937.0" GraphRef="cfc1d" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8980228" /> </Interaction> <Interaction GraphId="fd335"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="606.0" Y="286.0" GraphRef="c8603" RelX="0.0" RelY="1.0" /> <Point X="606.0" Y="312.0" GraphRef="b58c4" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-6785181" /> </Interaction> <Interaction GraphId="fd7e7"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="2339.0" Y="1142.0" GraphRef="da999" RelX="0.0" RelY="-1.0" /> <Point X="2335.0" Y="1104.0" GraphRef="a9b11" RelX="3.0" RelY="-0.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8865667" /> </Interaction> <Interaction GraphId="fd8e7"> <Comment Source="Reactome">Angiopoietin-like proteins (ANGPTLs) play major roles in the trafficking and metabolism of lipids. Angiopoietin-like protein 8 (ANGPTL8, aka betatrophin, lipasin) can regulate ANGPTL3 by binding to and promoting cleavage of it, thereby further activating ANGPTL3 (a protein that plays a critical role in the regulation of triglyceride and cholesterol plasma levels, via reversible inhibition of lipoprotein lipase activity) (Ren et al. 2012, Quagliarini et al. 2012, Li &amp; Teng 2014). The exact mechanism of action of ANGPTL8 on ANGPTL3 is poorly understood.</Comment> <BiopaxRef>f62</BiopaxRef> <BiopaxRef>e61</BiopaxRef> <BiopaxRef>df4</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="929.0" Y="141.0" /> <Point X="930.0" Y="207.0" /> <Anchor Position="0.0" Shape="None" GraphId="a4c9b" /> <Anchor Position="0.99" Shape="None" GraphId="d6eb7" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8856525" /> </Interaction> <Interaction GraphId="fddcd"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3900.0" Y="538.0" GraphRef="aa7d9" RelX="-1.0" RelY="0.0" /> <Point X="3879.0" Y="583.0" GraphRef="b78f6" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-264695" /> </Interaction> <Interaction GraphId="fdff0"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1467.0" Y="636.0" GraphRef="b23fd" RelX="0.7100000000000364" RelY="0.009999999999990905" /> <Point X="1485.0" Y="681.0" GraphRef="d66b2" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174690" /> </Interaction> <Interaction GraphId="fe3f6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="3413.0" Y="784.0" GraphRef="fde3a" RelX="1.0" RelY="-0.047619047619047616" /> <Point X="3430.0" Y="809.0" GraphRef="f4dcc" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-266303" /> </Interaction> <Interaction GraphId="fe8e7"> <Comment Source="Reactome">The second phase of chylomicron assembly takes place in the lumen of the endoplasmic reticulum. ApoB-48 continues to bind triacylglycerol, as well as cholesterol, cholesterol esters, and molecules of apolipoproteins A-I, A-II, and A-IV. 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