Translocation of SLC2A4 (GLUT4) to the plasma membrane (Homo sapiens)

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<?xml version="1.0" encoding="UTF-8"?> <Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="Translocation of GLUT4 to the plasma membrane" Organism="Homo sapiens"> <Comment Source="WikiPathways-description">In adipocytes and myocytes insulin signaling causes intracellular vesicles carrying the GLUT4 (SLC2A4) glucose transporter to translocate to the plasma membrane, allowing the cells to take up glucose from the bloodstream (reviewed in Zaid et al. 2008, Leney and Tavare 2009, Bogan and Kandror 2010, Foley et al. 2011, Hoffman and Elmendorf 2011, Kandror and Pilch 2011). In myocytes muscle contraction alone can also cause translocation of GLUT4.&lt;br&gt;Though the entire pathway leading to GLUT4 translocation has not been elucidated, several steps are known. Insulin activates the kinases AKT1 and AKT2. Muscle contraction activates the kinase AMPK-alpha2 and possibly also AKT. AKT2 and, to a lesser extent, AKT1 phosphorylate the RAB GTPase activators TBC1D1 and TBC1D4, causing them to bind 14-3-3 proteins and lose GTPase activation activity. As a result RAB proteins (probably RAB8A, RAB10, RAB14 and possibly RAB13) accumulate GTP. The connection between RAB:GTP and vesicle translocation is unknown but may involve recruitment and activation of myosins.&lt;br&gt;Myosins 1C, 2A, 2B, 5A, 5B have all been shown to play a role in translocating GLUT4 vesicles near the periphery of the cell. Following docking at the plasma membrane the vesicles fuse with the plasma membrane in a process that depends on interaction between VAMP2 on the vesicle and SNAP23 and SYNTAXIN-4 at the plasma membrane. 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As inferred from mouse, binding to 14-3-3 does not interfere with the interaction between AS160 and IRAP (LNPEP).</Comment> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Graphics CenterX="378.5" CenterY="442.0" Width="179.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1445133" /> </DataNode> <DataNode TextLabel="AMPK-alpha2:AMPK-beta:AMPK-gamma:AMP" GraphId="ae285" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="126.0" CenterY="682.0" Width="172.0" Height="42.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1454683" /> </DataNode> <DataNode TextLabel="GDP " GraphId="ae751" Type="Metabolite" GroupRef="a84fa"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1458466" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1437.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17552" /> </DataNode> <DataNode TextLabel="p-S486,S696,T715-RALGAPA2 " GraphId="ae81c" Type="Protein" GroupRef="b90f7"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1458472" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1357.0" Width="100.0" Height="40.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q2PPJ7" /> </DataNode> <DataNode TextLabel="SFN " GraphId="aeb4f" Type="Protein" GroupRef="fbba7"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1445138" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="100.0" CenterY="1217.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P31947" /> </DataNode> <DataNode TextLabel="RAB14 " GraphId="af5f5" Type="Protein" GroupRef="d3e0a"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1445130" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1097.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P61106" /> </DataNode> <DataNode TextLabel="p-S237-TBC1D1" GraphId="afdad" Type="Protein"> <Comment Source="Reactome">As inferred from rat L6 muscle cells, TBC1D1 is located in the perinuclear cytosol (Chen et al. 2008). TBC1D1 is observed throughout the cytosol and, based on its homology to TBC1D4 and its interaction with membrane-bound RAB proteins, TBC1D1 is expected to be concentrated near vesicle membranes.</Comment> <BiopaxRef>a10</BiopaxRef> <BiopaxRef>f11</BiopaxRef> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="238.5" CenterY="812.5" Width="101.0" Height="37.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q86TI0" /> </DataNode> <DataNode TextLabel="RALA " GraphId="b0e3c" Type="Protein" GroupRef="f27d1"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-2316343" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1417.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11233" /> </DataNode> <DataNode TextLabel="ASPSCR1" GraphId="b23fd" Type="Protein"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Graphics CenterX="1097.5" CenterY="852.0" Width="111.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9BZE9" /> </DataNode> <DataNode TextLabel="RAB11A:GTP" GraphId="b26bd" Type="Complex"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Graphics CenterX="1053.0" CenterY="551.0" Width="100.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1458542" /> </DataNode> <DataNode TextLabel="MYO1C " GraphId="b3f05" Type="Protein" GroupRef="d9228"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-2316345" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1657.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O00159" /> </DataNode> <DataNode TextLabel="CALM1 " GraphId="b4d58" Type="Protein" GroupRef="d9228"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-2316345" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1677.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P0DP23" /> </DataNode> <DataNode TextLabel="p-S1652-MYO5A:F-actin" GraphId="b6a4d" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1534.0" CenterY="435.0" Width="164.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-2316339" /> </DataNode> <DataNode TextLabel="p-S237-TBC1D1 " GraphId="b7a8c" Type="Protein" GroupRef="bbb43"> <Comment Source="Reactome">As inferred from rat L6 muscle cells, TBC1D1 is located in the perinuclear cytosol (Chen et al. 2008). TBC1D1 is observed throughout the cytosol and, based on its homology to TBC1D4 and its interaction with membrane-bound RAB proteins, TBC1D1 is expected to be concentrated near vesicle membranes.</Comment> <BiopaxRef>a10</BiopaxRef> <BiopaxRef>f11</BiopaxRef> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1454696" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="1257.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q86TI0" /> </DataNode> <DataNode TextLabel="YWHAZ " GraphId="b8b22" Type="Protein" GroupRef="fbba7"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1445138" /> <Attribute Key="copies_num" Value="6" /> <Graphics CenterX="100.0" CenterY="1257.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P63104" /> </DataNode> <DataNode TextLabel="MYH9" GraphId="b986d" Type="Protein"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1218.0" CenterY="641.0" Width="58.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P35579" /> </DataNode> <DataNode TextLabel="YWHAB " GraphId="b9a53" Type="Protein" GroupRef="e7f0a"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1445124" /> <Attribute Key="copies_num" Value="7" /> <Graphics CenterX="100.0" CenterY="1477.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P31946" /> </DataNode> <DataNode TextLabel="p-S237-TBC1D1:14-3-3" GraphId="ba34f" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="198.0" CenterY="934.0" Width="122.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1454696" /> </DataNode> <DataNode TextLabel="LNPEP " GraphId="baebc" Type="Protein" GroupRef="e7f0a"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1445124" /> <Attribute Key="copies_num" Value="8" /> <Graphics CenterX="100.0" CenterY="1517.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9UIQ6" /> </DataNode> <DataNode TextLabel="RGC1:p-486,696-T715-RGC2" GraphId="bb7bf" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="909.0" CenterY="229.5" Width="196.0" Height="25.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1458472" /> </DataNode> <DataNode TextLabel="p-S197-C2CD5 " GraphId="bca0b" Type="Protein" GroupRef="f42d3"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" 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Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-5260210" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="800.0" CenterY="1317.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:29108" /> </DataNode> <DataNode TextLabel="ADP" GraphId="ed926" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="854.0" CenterY="190.0" Width="40.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16761" /> </DataNode> <DataNode TextLabel="GLUT4:TUG" GraphId="edcfb" Type="Complex"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Graphics CenterX="908.0" CenterY="726.0" Width="104.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1449566" /> </DataNode> <DataNode TextLabel="MYO5A" GraphId="ee4e7" Type="Protein"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1552.0" CenterY="294.5" Width="60.0" Height="23.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9Y4I1" /> </DataNode> <DataNode TextLabel="p-AKT1,p-AKT2" GraphId="ef6ef" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="63.5" CenterY="296.0" Width="95.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-9023954" /> </DataNode> <DataNode TextLabel="p-T309,S474-AKT2 " GraphId="f0722" Type="Protein" GroupRef="eb629"> <BiopaxRef>b6f</BiopaxRef> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-9023954" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="1657.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P31751" /> </DataNode> <DataNode TextLabel="KIF3" GraphId="f1083" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1208.5" CenterY="234.0" Width="53.0" Height="24.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-2316334" /> </DataNode> <DataNode TextLabel="ADP" GraphId="f1ce3" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="1475.5" CenterY="112.0" Width="41.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:16761" /> </DataNode> <DataNode TextLabel="YWHAH " GraphId="f2ad7" Type="Protein" GroupRef="e857c"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1445138" /> <Attribute Key="copies_num" Value="2" /> <Graphics CenterX="520.0" CenterY="1057.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q04917" /> </DataNode> <DataNode TextLabel="14-3-3 dimer" GraphId="f2b9f" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="119.5" CenterY="812.0" Width="107.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="RoundedRectangle" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1445138" /> </DataNode> <DataNode TextLabel="YWHAG " GraphId="f3577" Type="Protein" GroupRef="e7f0a"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1445124" /> <Attribute Key="copies_num" Value="3" /> <Graphics CenterX="100.0" CenterY="1397.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P61981" /> </DataNode> <DataNode TextLabel="GTP " GraphId="f3596" Type="Metabolite" GroupRef="eb4df"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1458522" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1477.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15996" /> </DataNode> <DataNode TextLabel="EXOC4 " GraphId="f4822" Type="Protein" GroupRef="f27d1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-2316343" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1277.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96A65" /> </DataNode> <DataNode TextLabel="PRKAB2 " GraphId="f536a" Type="Protein" GroupRef="be016"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1454683" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="1097.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O43741" /> </DataNode> <DataNode TextLabel="GDP" GraphId="f5463" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Graphics CenterX="961.5" CenterY="642.0" Width="39.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17552" /> </DataNode> <DataNode TextLabel="p-Y521-STXBP3" GraphId="f58e6" Type="Protein"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="1585.0" CenterY="843.0" Width="110.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O00186" /> </DataNode> <DataNode TextLabel="EXOC2 " GraphId="f594b" Type="Protein" GroupRef="f27d1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-2316343" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1257.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96KP1" /> </DataNode> <DataNode TextLabel="RAB8A,10,13,14:GDP" GraphId="f66b1" Type="Complex"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Graphics CenterX="617.0" CenterY="590.0" Width="170.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1445130" /> </DataNode> <DataNode TextLabel="SFN " GraphId="f6e84" Type="Protein" GroupRef="e857c"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1445138" /> <Attribute Key="copies_num" Value="4" /> <Graphics CenterX="520.0" CenterY="1097.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P31947" /> </DataNode> <DataNode TextLabel="RGC1:RGC2" GraphId="f75a2" Type="Complex"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="653.5" CenterY="229.0" Width="101.0" Height="26.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1458509" /> </DataNode> <DataNode TextLabel="GTP " GraphId="f77ff" Type="Metabolite" GroupRef="f4406"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-217289" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="800.0" CenterY="1497.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15996" /> </DataNode> <DataNode TextLabel="RAB10 " GraphId="f780f" Type="Protein" GroupRef="a6208"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1445137" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="1457.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P61026" /> </DataNode> <DataNode TextLabel="RAB13 " GraphId="f78c9" Type="Protein" GroupRef="a6208"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1445137" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="1477.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P51153" /> </DataNode> <DataNode TextLabel="YWHAE " GraphId="f7caa" Type="Protein" GroupRef="e7f0a"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1445124" /> <Attribute Key="copies_num" Value="8" /> <Graphics CenterX="100.0" CenterY="1497.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P62258" /> </DataNode> <DataNode TextLabel="ATP" GraphId="f9345" Type="Metabolite"> <Attribute Key="cellular_location" Value="cytosol" /> <Graphics CenterX="934.0" CenterY="806.0" Width="40.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:15422" /> </DataNode> <DataNode TextLabel="p-5S,T642-TBC1D4 " GraphId="f9ceb" Type="Protein" GroupRef="bb082"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1445133" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="1117.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="O60343" /> </DataNode> <DataNode TextLabel="RAC1:GTP" GraphId="fae89" Type="Complex"> <BiopaxRef>d8b</BiopaxRef> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="1617.5" CenterY="613.0" Width="69.0" Height="22.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-217289" /> </DataNode> <DataNode TextLabel="TBC1D1" GraphId="fb022" Type="Protein"> <Comment Source="Reactome">As inferred from rat L6 muscle cells, TBC1D1 is located in the perinuclear cytosol (Chen et al. 2008). TBC1D1 is observed throughout the cytosol and, based on its homology to TBC1D4 and its interaction with membrane-bound RAB proteins, TBC1D1 is expected to be concentrated near vesicle membranes.</Comment> <BiopaxRef>a10</BiopaxRef> <BiopaxRef>f1c</BiopaxRef> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Graphics CenterX="325.5" CenterY="592.0" Width="65.0" Height="30.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q86TI0" /> </DataNode> <DataNode TextLabel="EXOC7 " GraphId="fb154" Type="Protein" GroupRef="f27d1"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-2316343" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1397.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9UPT5" /> </DataNode> <DataNode TextLabel="STX4:STXBP3&#xA;(MUNC18C)" GraphId="fbd8c" Type="Complex"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Graphics CenterX="803.5" CenterY="971.0" Width="91.0" Height="36.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-2263479" /> </DataNode> <DataNode TextLabel="RALA:GDP" GraphId="fbfc4" Type="Complex"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Graphics CenterX="657.5" CenterY="420.5" Width="79.0" Height="25.0" ZOrder="32768" FontSize="10" Valign="Middle" ShapeType="Hexagon" Color="a52a2a" /> <Xref Database="Reactome" ID="R-HSA-1458466" /> </DataNode> <DataNode TextLabel="RAB8A " GraphId="fc45f" Type="Protein" GroupRef="d3e0a"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1445130" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1117.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P61006" /> </DataNode> <DataNode TextLabel="RALA " GraphId="fcc20" Type="Protein" GroupRef="a84fa"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1458466" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="520.0" CenterY="1417.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P11233" /> </DataNode> <DataNode TextLabel="f-actin (ADP) " GraphId="fda5f" GroupRef="f27d1"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-2316343" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1457.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Reactome" ID="R-HSA-202998" /> </DataNode> <DataNode TextLabel="YWHAZ " GraphId="fdfd4" Type="Protein" GroupRef="e857c"> <Attribute Key="cellular_location" Value="cytosol" /> <Attribute Key="complex_id" Value="R-HSA-1445138" /> <Attribute Key="copies_num" Value="6" /> <Graphics CenterX="520.0" CenterY="1137.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P63104" /> </DataNode> <DataNode TextLabel="EXOC4 " GraphId="fe9e1" Type="Protein" GroupRef="c96fe"> <Attribute Key="cellular_location" Value="plasma membrane" /> <Attribute Key="complex_id" Value="R-HSA-264974" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="660.0" CenterY="1077.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q96A65" /> </DataNode> <DataNode TextLabel="ASPSCR1 " GraphId="ff95b" Type="Protein" GroupRef="b7642"> <Attribute Key="cellular_location" Value="cytoplasmic vesicle membrane" /> <Attribute Key="complex_id" Value="R-HSA-1449566" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="380.0" CenterY="1197.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9BZE9" /> </DataNode> <Interaction GraphId="a0c2d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1105.0" Y="415.0" GraphRef="cc68a" RelX="1.0" RelY="0.0" /> <Point X="1164.0" Y="430.0" GraphRef="de502" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316349" /> </Interaction> <Interaction GraphId="a3f90"> <Comment Source="Reactome">RALA is a guanine nucleotide binding protein that hydrolyzes bound GTP to yield GDP and phosphate. RGC1 and RGC2 are GAPs (GTPase-activating proteins) that activate the GTPase activity of RALA. Insulin activates AKT, which phosphorylates RGC2, inactivating the GAP activity of RGC1:RGC2 and allowing RALA:GTP to accumulate.</Comment> <BiopaxRef>efb</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1014.0" Y="407.0" /> <Point X="768.0" Y="390.0" /> <Anchor Position="0.0" Shape="None" GraphId="e0e4b" /> <Anchor Position="0.99" Shape="None" GraphId="bcaff" /> <Anchor Position="0.5" Shape="None" GraphId="ec981" /> <Anchor Position="0.5" Shape="None" GraphId="be5f2" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1458485" /> </Interaction> <Interaction GraphId="a4aa8"> <Comment Source="Reactome">The protein kinase B beta (AKT) pathway mediates insulin-stimulated glucose transport by increasing glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. C2 domain-containing protein 5 (C2CD5 aka C2 domain-containing phosphoprotein 138kDa) has been shown to be required for optimal insulin-stimulated GLUT4 translocation and fusion of GLUT4 vesicles with the plasma membrane in adipocytes. It is also able to bind Ca2+ and lipid membranes in its C2 domain. C2CD5 is a substrate for RAC-beta serine/threonine-protein kinase (AKT2), which phosphorylates C2CD5 at serine 197. Phosphorylated C2CD5 optimises GLUT4 translocation to the plasma membrane. The role of human C2CD5 is inferred from the role of the orthologous mouse protein (Xie et al. 2011).</Comment> <BiopaxRef>ef8</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1312.0" Y="112.0" /> <Point X="1397.0" Y="112.0" /> <Anchor Position="0.0" Shape="None" GraphId="d6d27" /> <Anchor Position="0.99" Shape="None" GraphId="e26d1" /> <Anchor Position="0.5" Shape="None" GraphId="f5891" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5260201" /> </Interaction> <Interaction GraphId="a6d5d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="832.0" Y="25.0" GraphRef="a06dc" RelX="1.0" RelY="0.0" /> <Point X="1548.0" Y="360.0" GraphRef="a5e3f" RelX="-0.5" RelY="-3.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449597" /> </Interaction> <Interaction GraphId="a7e54"> <Comment Source="Reactome">As inferred from mouse, GLUT4 (SLC2A4) initially translocates from endosomes to insulin-responsive vesicles (IRVs, GSVs). RAB11 appears to play a role in this process. IRVs bearing GLUT4 are then translocated across the cortical actin network to the plasma membrane. Unconventional myosin 5A (MYO5A) interacts with RAB10 or RAB8A on the vesicle and participates in transport of the IRV. Myosin 1C appears to act close to the plasma membrane and may facilitate fusion of the vesicle with the plasma membrane. RAB:GTP complexes coupled to the vesicles may interact with myosins to regulate their activity. Non-muscle myosin IIA (MYH9) appears to interact with the SNAP23 complex to dock the IRV at the inner membrane face.</Comment> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1379.0" Y="561.0" /> <Point X="1373.0" Y="701.0" /> <Anchor Position="0.0" Shape="None" GraphId="b3f39" /> <Anchor Position="0.99" Shape="None" GraphId="bc6a1" /> <Anchor Position="0.5" Shape="None" GraphId="deb2c" /> <Anchor Position="0.5" Shape="None" GraphId="b58b5" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316352" /> </Interaction> <Interaction GraphId="aad4d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="954.0" Y="806.0" GraphRef="f9345" RelX="1.0" RelY="0.0" /> <Point X="1089.0" Y="763.0" GraphRef="ffd09" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449574" /> </Interaction> <Interaction GraphId="ab8ac"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1508.0" Y="299.0" GraphRef="be6ce" RelX="1.0" RelY="0.0" /> <Point X="1547.0" Y="339.0" GraphRef="ed6cd" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449597" /> </Interaction> <Interaction GraphId="ac9bd"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="931.0" Y="970.0" GraphRef="d337f" RelX="0.9733333333333334" RelY="-0.030303030303030304" /> <Point X="1089.0" Y="763.0" GraphRef="ffd09" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449574" /> </Interaction> <Interaction GraphId="b03f6"> <Comment Source="Reactome">TBC1D1 phosphorylated on serine-237 binds 14-3-3 proteins in assays with yeast 14-3-3 proteins BMH1 and BMH2 (Chen et al. 2008, Frosig et al. 2010). Binding with human 14-3-3 proteins is inferred.</Comment> <BiopaxRef>a10</BiopaxRef> <BiopaxRef>fad</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="205.0" Y="843.0" /> <Point X="200.0" Y="913.0" /> <Anchor Position="0.0" Shape="None" GraphId="a0251" /> <Anchor Position="0.99" Shape="None" GraphId="a82ba" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1454689" /> </Interaction> <Interaction GraphId="b12e8"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1550.0" Y="387.0" GraphRef="a5dfd" RelX="0.029999999999972715" RelY="0.4800000000000182" /> <Point X="1503.0" Y="396.0" GraphRef="a82d1" RelX="0.9512195121951219" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449597" /> </Interaction> <Interaction GraphId="b313e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1481.0" Y="769.0" GraphRef="f4a18" RelX="3.9200000000000728" RelY="0.05999999999994543" /> <Point X="1570.0" Y="760.0" GraphRef="aa095" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449574" /> </Interaction> <Interaction GraphId="b3cab"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="110.0" Y="296.0" GraphRef="ef6ef" RelX="0.9789473684210527" RelY="0.0" /> <Point X="295.0" Y="361.0" GraphRef="ae5f1" RelX="-1.0" RelY="-1.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1445144" /> </Interaction> <Interaction GraphId="b3fab"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1259.0" Y="255.0" GraphRef="e6c4e" RelX="-1.0" RelY="-0.04" /> <Point X="1207.0" Y="274.0" GraphRef="ac93f" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316347" /> </Interaction> <Interaction GraphId="b454a"> <Comment Source="Reactome">After docking at the membrane VAMP2 on the vesicle interacts with SYNTAXIN-4 and SNAP23 on the plasma membrane to catalyze fusion of the vesicle with the plasma membrane. 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Motor activity of Kif3 along microtubules is believed to transport vesicles containing Glut4 (Slc2a4) across the cytosol to the cortical actin network.</Comment> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1207.0" Y="274.0" /> <Point X="1207.0" Y="339.0" /> <Anchor Position="0.0" Shape="None" GraphId="ac93f" /> <Anchor Position="0.99" Shape="None" GraphId="fb3d6" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316347" /> </Interaction> <Interaction GraphId="bcb33"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="273.0" Y="287.0" GraphRef="c2e88" RelX="1.0" RelY="0.0" /> <Point X="296.0" Y="323.0" GraphRef="fe02b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1445144" /> </Interaction> <Interaction GraphId="bd2e6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1452.0" Y="435.0" GraphRef="b6a4d" RelX="-1.0" RelY="0.0" /> <Point X="1373.0" Y="609.0" GraphRef="deb2c" RelX="-3.0" RelY="-22.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316352" /> </Interaction> <Interaction GraphId="bd4c8"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="768.0" Y="390.0" GraphRef="bcaff" RelX="-2.4600000000000364" RelY="-0.17000000000001592" /> <Point X="731.0" Y="380.0" GraphRef="a653c" RelX="0.9259259259259259" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1458485" /> </Interaction> <Interaction GraphId="be754"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1284.0" Y="112.0" GraphRef="e3bf3" RelX="1.0" RelY="0.0" /> <Point X="1312.0" Y="112.0" GraphRef="d6d27" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-5260201" /> </Interaction> <Interaction GraphId="bf83f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1397.0" Y="112.0" GraphRef="e26d1" 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ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="953.0" Y="439.0" GraphRef="a9f58" RelX="1.8500000000000227" RelY="-0.01999999999998181" /> <Point X="995.0" Y="459.0" GraphRef="ca914" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2255342" /> </Interaction> <Interaction GraphId="c781c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="792.0" Y="206.0" GraphRef="ec68f" RelX="0.4700000000000273" RelY="0.0" /> <Point X="834.0" Y="190.0" GraphRef="ed926" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1458463" /> </Interaction> <Interaction GraphId="c8034"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1373.0" Y="701.0" GraphRef="bc6a1" RelX="-0.05999999999994543" RelY="1.3999999999999773" /> <Point X="1374.0" Y="704.0" GraphRef="ddc8a" RelX="-0.0018832391713747645" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316352" /> </Interaction> <Interaction GraphId="c81fe"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1550.0" Y="387.0" GraphRef="a5dfd" RelX="0.029999999999972715" RelY="0.4800000000000182" /> <Point X="1534.0" Y="420.0" GraphRef="b6a4d" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449597" /> </Interaction> <Interaction GraphId="c88cf"> <Comment Source="Reactome">As inferred from mouse, AKT2 (PKB-beta) phosphorylates RBC2 (RALGAPA2) on serine-486, serine-696, and threonine-715 in response to insulin. The phosphorylation prevents RBC1:RBC2 from activating RALA GTPase and allows RALA:GTP to accumulate.</Comment> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="745.0" Y="206.0" /> <Point X="792.0" Y="206.0" /> <Anchor Position="0.0" Shape="None" GraphId="df07c" /> <Anchor Position="0.99" Shape="None" GraphId="ec68f" /> <Anchor Position="0.5" Shape="None" GraphId="ca3e7" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1458463" /> </Interaction> <Interaction GraphId="ca2c3"> <Comment Source="Reactome">As inferred from mouse, AKT2 phosphorylates Myosin 5A on serine-1652. The phosphorylation promotes association of Myosin 5A with actin and ATPase activity of Myosin 5A.</Comment> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1547.0" Y="339.0" /> <Point X="1550.0" Y="387.0" /> <Anchor Position="0.0" Shape="None" GraphId="ed6cd" /> <Anchor Position="0.99" Shape="None" GraphId="a5dfd" /> <Anchor Position="0.5" Shape="None" GraphId="a5e3f" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449597" /> </Interaction> <Interaction GraphId="ca8ec"> <Comment Source="Reactome">In response to muscle contraction and insulin signaling, AMPK-alpha2 phosphorylates TBC1D1 on serine 237 and probably other residues (Frosig et al. 2010, Vichaiwong et al. 2010). As inferred from rat L6 muscle cells TBC1D1 colocalizes with perinuclear vesicles bearing GLUT4 (SLC2A4) and may be involved in an early step that mobilizes them (Chen et al. 2008). Human TBC1D1 appears cytosolic and is believed to be concentrated near vesicle membranes (Park et al. 2011).</Comment> <BiopaxRef>fad</BiopaxRef> <BiopaxRef>f11</BiopaxRef> <BiopaxRef>a10</BiopaxRef> <BiopaxRef>f1c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="235.0" Y="655.0" /> <Point X="236.0" Y="755.0" /> <Anchor Position="0.0" Shape="None" GraphId="a089e" /> <Anchor Position="0.99" Shape="None" GraphId="e3e26" /> <Anchor Position="0.5" Shape="None" GraphId="b51f2" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1454699" /> </Interaction> <Interaction GraphId="cbb15"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1552.0" Y="305.0" GraphRef="ee4e7" RelX="0.0" RelY="0.9130434782608695" /> <Point X="1547.0" Y="339.0" GraphRef="ed6cd" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449597" /> </Interaction> <Interaction GraphId="cd42c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1387.0" Y="340.0" GraphRef="d3052" RelX="-1.0" RelY="0.0" /> <Point X="1164.0" Y="430.0" GraphRef="de502" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316349" /> </Interaction> <Interaction GraphId="ce3f9"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1107.0" Y="595.0" /> <Point X="1373.0" Y="609.0" GraphRef="b58b5" RelX="-3.0" RelY="-22.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316352" /> </Interaction> <Interaction GraphId="ce60c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="744.0" Y="462.0" GraphRef="a6e4d" RelX="1.0" RelY="0.0" /> <Point X="768.0" Y="441.0" GraphRef="ac01b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2255342" /> </Interaction> <Interaction GraphId="cfe1e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1452.0" Y="435.0" GraphRef="d7ca4" RelX="4.609756097560975" RelY="-3.4444444444444446" /> <Point X="1373.0" Y="609.0" GraphRef="deb2c" RelX="-3.0" RelY="-22.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316352" /> </Interaction> <Interaction GraphId="d0002"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1207.0" Y="339.0" GraphRef="fb3d6" RelX="0.0" RelY="0.6499999999999773" /> <Point X="1207.0" Y="342.0" GraphRef="a1a8e" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2316347" /> </Interaction> <Interaction GraphId="d0408"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1481.0" Y="769.0" GraphRef="f4a18" RelX="3.9200000000000728" RelY="0.05999999999994543" /> <Point X="1565.0" Y="800.0" GraphRef="c49f9" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449574" /> </Interaction> <Interaction GraphId="d1694"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1481.0" Y="769.0" GraphRef="f4a18" RelX="3.9200000000000728" RelY="0.05999999999994543" /> <Point X="1530.0" Y="843.0" GraphRef="f58e6" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1449574" /> </Interaction> <Interaction GraphId="d1704"> <Comment Source="Reactome">RAB proteins have intrinsic weak GTPase activity that is enhanced by RAB-GTPase activating proteins (RAB-GAPs, Sano et al. 2007). The GTPase activity of RAB13 is inferred from other RAB proteins. AS160 (TBC1D4) and TBC1D1 are GAPs that activate the GTPase activity of RAB8A/10/13. 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">19389739</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Leney SE, Tavaré JM.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="cf1"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">17369524</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Resistance exercise and insulin regulate AS160 and interaction with 14-3-3 in human skeletal muscle.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Howlett KF, Sakamoto K, Garnham A, Cameron-Smith D, Hargreaves M.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="e97"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">15919790</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Karlsson HK, Zierath JR, Kane S, Krook A, Lienhard GE, Wallberg-Henriksson H.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="dbf"> <bp:ID 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Chen S, Murphy J, Toth R, Campbell DG, Morrice NA, Mackintosh C.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="ab6"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">19013499</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Ngo S, Barry JB, Nisbet JC, Prins JB, Whitehead JP.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="f11"> <bp:ID 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