Transport of bile salts and organic acids, metal ions and amine compounds (Homo sapiens)

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<?xml version="1.0" encoding="UTF-8"?> <Pathway xmlns="http://genmapp.org/GPML/2010a" Name="Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds" Organism="Homo sapiens" Data-Source="Reactome - http://www.reactome.org" Version="release 35" Author="Jassal, B" Maintainer="Jassal, B"> <Comment Source="WikiPathways-description">Hexoses like glucose, galactose and fructose serve as basic fuel molecules for eukaryotic cells. Indeed, glucose is the main energy source for mammalian cells. These sugars are unable to diffuse across cellular membranes, and require transporter proteins for entry into and exit out of cells. Four gene families encode hexose transporter proteins (He et al, 2009). SLC2 family contains 14 genes and encode facilitative glucose transporters (GLUTs) (Uldry M and Thorens B, 2004). SLC5 family contains 12 genes and encode Na+/glucose symporters (Wright EM and Turk E, 2004). SLC37 family contains 4 members and encode sugar-phosphate/phosphate exchangers (Bartoloni L and Antonarakis SE, 2004). SLC45 family has 4 members and encode putative sugar/H+ symporters.</Comment> <Comment Source="WikiPathways-category">Cellular Process</Comment> <BiopaxRef>lit_427985</BiopaxRef> <BiopaxRef>lit_428756</BiopaxRef> <BiopaxRef>lit_428758</BiopaxRef> <BiopaxRef>lit_428761</BiopaxRef> <DataNode GraphId="n1_REACTOME_446597" TextLabel="MATE substrates&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="2717.5" CenterY="260.5" Width="109.0" Height="31.0" Valign="Middle" FillColor="ccffcc" ShapeType="Oval"/> <Xref Database="Reactome" ID="REACT_20849"/> </DataNode> <DataNode GraphId="n2_REACTOME_437295" TextLabel="Copper&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="2237.5" CenterY="102.5" Width="57.0" Height="31.0" Valign="Middle" FillColor="ccffcc" ShapeType="Oval"/> <Xref Database="ChEBI" ID="28694"/> </DataNode> <DataNode GraphId="n3_REACTOME_264638" TextLabel="Choline&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="1425.5" CenterY="59.5" Width="59.0" 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<DataNode GraphId="n46_REACTOME_70113" TextLabel="alpha-D-glucose&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="1007.0" CenterY="236.5" Width="108.0" Height="31.0" Valign="Middle" FillColor="ccffcc" ShapeType="Oval"/> <Xref Database="ChEBI" ID="17925"/> </DataNode> <DataNode GraphId="n47_REACTOME_189246" TextLabel="fructose, galactose, &#10;glucose&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="786.0" CenterY="231.0" Width="126.0" Height="46.0" Valign="Middle" FillColor="ccffcc" ShapeType="Oval"/> <Xref Database="Reactome" ID="REACT_9838"/> </DataNode> <DataNode GraphId="n48_REACTOME_428789" TextLabel="Class I GLUTs&#10;" Type="Unknown"> <Graphics Color="000000" CenterX="1098.5" CenterY="161.5" Width="89.0" Height="23.0" Valign="Middle" FillColor="ccffcc"/> <Xref Database="Reactome" ID="REACT_20111"/> </DataNode> <DataNode GraphId="n49_REACTOME_70115" TextLabel="alpha-D-glucose&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="1003.0" CenterY="94.5" 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CenterY="481.5" Width="112.0" Height="61.0" Valign="Middle" FillColor="ccffcc" ShapeType="Oval"/> <Xref Database="Reactome" ID="REACT_21050"/> </DataNode> <DataNode GraphId="n149_REACTOME_374935" TextLabel="Noradrenaline&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="3481.5" CenterY="916.5" Width="95.0" Height="31.0" Valign="Middle" FillColor="ccffcc" ShapeType="Oval"/> <Xref Database="ChEBI" ID="18357"/> </DataNode> <DataNode GraphId="n150_REACTOME_375458" TextLabel="ligands of SLC6A19&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="4299.5" CenterY="25.5" Width="125.0" Height="31.0" Valign="Middle" FillColor="ccffcc" ShapeType="Oval"/> <Xref Database="Reactome" ID="REACT_15160"/> </DataNode> <DataNode GraphId="n151_REACTOME_352024" TextLabel="ligands of SLC6A6&#10;" Type="Metabolite"> <Graphics Color="000000" CenterX="4540.0" CenterY="1000.5" Width="118.0" Height="31.0" Valign="Middle" FillColor="ccffcc" ShapeType="Oval"/> <Xref Database="Reactome" 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Too much influx results in cell poisoning. In humans, there are two member of the SLC31 gene family that are implicated in copper transport. The human gene SLC31A1 encodes human copper transporter 1, hCTR1 and is ubiquitiously expressed, with highest levels seen in the liver.. It was first identified by functional complementation in ctr1-deficient yeast (Zhou B and Gitschier J, 1997). hCTR1 exists as a homotrimer at the plasma membrane of cells (De Feo CJ et al, 2007) and is responsible for high-affinity copper uptake (Lee J et al, 2002). The second gene product, hCTR2, has not be characterized yet.</Comment> <BiopaxRef>lit_437298</BiopaxRef> <BiopaxRef>lit_437294</BiopaxRef> <BiopaxRef>lit_437289</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2236.0" Y="121.0" GraphId="e_239_0" GraphRef="n2_REACTOME_437295" RelX="-0.03508771929824561" RelY="1.2258064516129032"/> <Point X="2236.0" Y="160.0" GraphId="e_239_1"/> <Point X="2236.0" Y="230.0" GraphId="e_239_2" GraphRef="n26_REACTOME_209799" RelX="-0.03508771929824561" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.3577981651376147" GraphId="e_239_a_p"/> </Graphics> </Line> <Line GraphId="e_239_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="2209.0" Y="158.0" GraphId="e_239_c__0_0" GraphRef="n24_REACTOME_437299" RelX="1.148936170212766" RelY="0.08695652173913043"/> <Point X="2236.0" Y="160.0" GraphId="e_239_c__0_1" GraphRef="e_239_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_240_REACTOME_442368"> <Comment Source="WikiPathways-description">The primary site for absorption of dietary iron is the duodenum. Ferrous iron (Fe2+) is taken up from the gut lumen across the apical membranes of enterocytes and released into the portal vein circulation across basolateral membranes.&lt;br&gt;The human gene SLC40A1 encodes a metal transporter protein MTP1 (also called ferroportin or IREG1). This protein resides on the basolateral membrane of enterocytes and mediates ferrous iron efflux into the portal vein (Schimanski LM et al, 2005). MTP1 colocalizes with hephaestin (HEPH) which stablizes MTP1 and is necessary for the efflux reaction to occur (Han O and Kim EY, 2007; Chen H et al, 2009). As well as the dudenum, MTP1 is also highly expressed on macrophages (where it mediates iron efflux from the breakdown of haem) and the placenta (where it may mediate the transport of iron from maternal to foetal circulation). It is also expressed in muscle and spleen.</Comment> <BiopaxRef>lit_442331</BiopaxRef> <BiopaxRef>lit_904846</BiopaxRef> <BiopaxRef>lit_904844</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2134.0" Y="107.0" GraphId="e_240_0" GraphRef="n447_REACTOME_912516" RelX="0.0" RelY="1.2258064516129032"/> <Point X="2134.0" Y="155.0" GraphId="e_240_1"/> <Point X="2133.0" Y="216.0" GraphId="e_240_2" GraphRef="n448_REACTOME_912519" RelX="0.0" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.44033386191295604" GraphId="e_240_a_p"/> </Graphics> </Line> <Line GraphId="e_240_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="2113.0" Y="156.0" GraphId="e_240_c__0_0" GraphRef="n449_REACTOME_904821" RelX="1.0642201834862386" RelY="-0.15789473684210525"/> <Point X="2134.0" Y="155.0" GraphId="e_240_c__0_1" GraphRef="e_240_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_241_REACTOME_435349"> <Comment Source="WikiPathways-description">The primary site for absorption of dietary iron is the duodenum. Ferrous iron (Fe2+) is taken up from the gut lumen across the apical membranes of enterocytes and released into the portal vein circulation across basolateral membranes.&lt;br&gt;The human gene SLC11A2 encodes the divalent cation transporter DCT1 (NRAMP2, Natural resistance-associated macrophage protein 2). NRAMP2 resides on the apical membrane of enterocytes and mediates the uptake of ferrous iron into these cells (Tandy S et al, 2000). DCT1 can also accept a broad range of transition metal ions.</Comment> <BiopaxRef>lit_435376</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2339.0" Y="198.0" GraphId="e_241_0"/> <Point X="2339.0" Y="161.0" GraphId="e_241_1"/> <Point X="2339.0" Y="114.0" GraphId="e_241_2"/> <Anchor Position="0.0" GraphId="e_241_a_i"/> <Anchor Position="0.44047619047619047" GraphId="e_241_a_p"/> <Anchor Position="1.0" GraphId="e_241_a_o"/> </Graphics> </Line> <Line GraphId="e_241_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2363.0" Y="198.0" GraphId="e_241_i0_0" GraphRef="n11_REACTOME_351626" RelX="-1.1875" RelY="0.0"/> <Point X="2339.0" Y="198.0" GraphId="e_241_i0_1" GraphRef="e_241_a_i"/> </Graphics> </Line> <Line GraphId="e_241_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2339.0" Y="236.0" GraphId="e_241_i1_0" GraphRef="n39_REACTOME_435347" RelX="-0.022988505747126436" RelY="-1.1612903225806452"/> <Point X="2339.0" Y="198.0" GraphId="e_241_i1_1" GraphRef="e_241_a_i"/> </Graphics> </Line> <Line GraphId="e_241_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2376.0" Y="114.0" GraphId="e_241_o0_0" ArrowHead="Arrow" GraphRef="n14_REACTOME_70106" RelX="-1.1875" RelY="-0.06451612903225806"/> <Point X="2339.0" Y="114.0" GraphId="e_241_o0_1" GraphRef="e_241_a_o"/> </Graphics> </Line> <Line GraphId="e_241_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2339.0" Y="72.0" GraphId="e_241_o1_0" ArrowHead="Arrow" GraphRef="n38_REACTOME_71067" RelX="0.0" RelY="1.2258064516129032"/> <Point X="2339.0" Y="114.0" GraphId="e_241_o1_1" GraphRef="e_241_a_o"/> </Graphics> </Line> <Line GraphId="e_241_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="2312.0" Y="161.0" GraphId="e_241_c__0_0" GraphRef="n25_REACTOME_435359" RelX="1.15" RelY="0.0"/> <Point X="2339.0" Y="161.0" GraphId="e_241_c__0_1" GraphRef="e_241_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_242_REACTOME_433089"> <Comment Source="WikiPathways-description">The human SLC10A6 gene encodes a sodium-dependant organic anion transporter, SOAT. Highest expressions of the gene are in testis, placenta and pancreas. Unlike the other SLC10A gene products, SOAT shows no affinity for binding bile acids. However, SOAT is able to transport sulpho-conjugated bile acids such as taurolithocholate 3-sulphate (Geyer J et al, 2007). It can also transport the structurally similar sulphated steroids (not shown here), thus SOAT may play a role in delivery of these prohormones to testis, pancreas and placenta.</Comment> <BiopaxRef>lit_433121</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1640.0" Y="117.0" GraphId="e_242_0"/> <Point X="1640.0" Y="159.0" GraphId="e_242_1"/> <Point X="1640.0" Y="203.0" GraphId="e_242_2"/> <Anchor Position="0.0" GraphId="e_242_a_i"/> <Anchor Position="0.4883720930232558" GraphId="e_242_a_p"/> <Anchor Position="1.0" GraphId="e_242_a_o"/> </Graphics> </Line> <Line GraphId="e_242_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1640.0" Y="97.0" GraphId="e_242_i0_0" GraphRef="n18_REACTOME_433120" RelX="0.0" RelY="1.1304347826086956"/> <Point X="1640.0" Y="117.0" GraphId="e_242_i0_1" GraphRef="e_242_a_i"/> </Graphics> </Line> <Line GraphId="e_242_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1675.0" Y="117.0" GraphId="e_242_i1_0" GraphRef="n27_REACTOME_74113" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="1640.0" Y="117.0" GraphId="e_242_i1_1" GraphRef="e_242_a_i"/> </Graphics> </Line> <Line GraphId="e_242_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1640.0" Y="248.0" GraphId="e_242_o0_0" ArrowHead="Arrow" GraphRef="n6_REACTOME_176483" RelX="0.0" RelY="-1.1304347826086956"/> <Point X="1640.0" Y="203.0" GraphId="e_242_o0_1" GraphRef="e_242_a_o"/> </Graphics> </Line> <Line GraphId="e_242_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1677.0" Y="204.0" GraphId="e_242_o1_0" ArrowHead="Arrow" GraphRef="n36_REACTOME_83910" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="1640.0" Y="203.0" GraphId="e_242_o1_1" GraphRef="e_242_a_o"/> </Graphics> </Line> <Line GraphId="e_242_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1612.0" Y="158.0" GraphId="e_242_c__0_0" GraphRef="n28_REACTOME_433091" RelX="1.1794871794871795" RelY="0.0"/> <Point X="1640.0" Y="159.0" GraphId="e_242_c__0_1" GraphRef="e_242_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_243_REACTOME_435171"> <Comment Source="WikiPathways-description">Natural resistance-associated macrophage proteins (NRAMPs) regulates macrophage activation for antimicrobial activity against intracellular pathogens. They do this by mediating metal ion transport across macrophage membranes and the subsequent use of these ions in the control of free radical formation.&lt;br&gt;The human gene SLC11A1 encodes NRAMP1 (Kishi F, 2004; Kishi F and Nobumoto M, 1995) which can utilize the protonmotive force to mediate divalent iron (Fe2+), zinc (Zn2+) and manganese (Mn2+) influx to or efflux from phagosomes.</Comment> <BiopaxRef>lit_435365</BiopaxRef> <BiopaxRef>lit_435173</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1722.0" Y="432.0" GraphId="e_243_0"/> <Point X="1782.0" Y="432.0" GraphId="e_243_1"/> <Point X="1851.0" Y="432.0" GraphId="e_243_2"/> <Anchor Position="0.0" GraphId="e_243_a_i"/> <Anchor Position="0.46511627906976744" GraphId="e_243_a_p"/> <Anchor Position="1.0" GraphId="e_243_a_o"/> </Graphics> </Line> <Line GraphId="e_243_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1659.0" Y="432.0" GraphId="e_243_i0_0" GraphRef="n9_REACTOME_445829" RelX="1.0576923076923077" RelY="-0.03278688524590164"/> <Point X="1722.0" Y="432.0" GraphId="e_243_i0_1" GraphRef="e_243_a_i"/> </Graphics> </Line> <Line GraphId="e_243_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1859.0" Y="404.0" GraphId="e_243_i1_0" GraphRef="n4_REACTOME_425999" RelX="0.0" RelY="1.2258064516129032"/> <Point X="1859.0" Y="432.0" GraphId="e_243_i1_1"/> <Point X="1722.0" Y="432.0" GraphId="e_243_i1_2" GraphRef="e_243_a_i"/> </Graphics> </Line> <Line GraphId="e_243_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1921.0" Y="432.0" GraphId="e_243_o0_0" ArrowHead="Arrow" GraphRef="n19_REACTOME_445832" RelX="-1.0576923076923077" RelY="-0.03278688524590164"/> <Point X="1851.0" Y="432.0" GraphId="e_243_o0_1" GraphRef="e_243_a_o"/> </Graphics> </Line> <Line GraphId="e_243_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1708.0" Y="398.0" GraphId="e_243_o1_0" ArrowHead="Arrow" GraphRef="n42_REACTOME_70106" RelX="-0.0625" RelY="1.2258064516129032"/> <Point X="1708.0" Y="432.0" GraphId="e_243_o1_1"/> <Point X="1851.0" Y="432.0" GraphId="e_243_o1_2" GraphRef="e_243_a_o"/> </Graphics> </Line> <Line GraphId="e_243_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1780.0" Y="406.0" GraphId="e_243_c__0_0" GraphRef="n7_REACTOME_437103" RelX="0.0" RelY="1.3043478260869565"/> <Point X="1782.0" Y="432.0" GraphId="e_243_c__0_1" GraphRef="e_243_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_244_REACTOME_429594"> <Comment Source="WikiPathways-description">The human SLC5A7 gene encodes a sodium- and chloride-dependent, high affinity choline transporter, CHT (Apparsundaram S et al, 2000). CHT transports choline from the extracellular space into neuronal cells and is dependent on Na+ and Cl- ions for transport (Okuda T and Haga T, 2000). Choline uptake is the rate-limiting step in acetylcholine synthesis.</Comment> <BiopaxRef>lit_429642</BiopaxRef> <BiopaxRef>lit_372536</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1424.0" Y="123.0" GraphId="e_244_0"/> <Point X="1424.0" Y="161.0" GraphId="e_244_1"/> <Point X="1424.0" Y="192.0" GraphId="e_244_2"/> <Anchor Position="0.0" GraphId="e_244_a_i"/> <Anchor Position="0.5507246376811594" GraphId="e_244_a_p"/> <Anchor Position="1.0" GraphId="e_244_a_o"/> </Graphics> </Line> <Line GraphId="e_244_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1424.0" Y="78.0" GraphId="e_244_i0_0" GraphRef="n3_REACTOME_264638" RelX="-0.03389830508474576" RelY="1.2258064516129032"/> <Point X="1424.0" Y="123.0" GraphId="e_244_i0_1" GraphRef="e_244_a_i"/> </Graphics> </Line> <Line GraphId="e_244_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1404.0" Y="115.0" GraphId="e_244_i1_0" GraphRef="n21_REACTOME_188972" RelX="1.1111111111111112" RelY="0.6451612903225806"/> <Point X="1424.0" Y="123.0" GraphId="e_244_i1_1" GraphRef="e_244_a_i"/> </Graphics> </Line> <Line GraphId="e_244_i2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1445.0" Y="116.0" GraphId="e_244_i2_0" GraphRef="n37_REACTOME_74113" RelX="-1.0769230769230769" RelY="0.7096774193548387"/> <Point X="1424.0" Y="123.0" GraphId="e_244_i2_1" GraphRef="e_244_a_i"/> </Graphics> </Line> <Line GraphId="e_244_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1454.0" Y="208.0" GraphId="e_244_o0_0" ArrowHead="Arrow" GraphRef="n8_REACTOME_83910" RelX="-0.6666666666666666" RelY="-1.1612903225806452"/> <Point X="1424.0" Y="192.0" GraphId="e_244_o0_1" GraphRef="e_244_a_o"/> </Graphics> </Line> <Line GraphId="e_244_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1424.0" Y="237.0" GraphId="e_244_o1_0" ArrowHead="Arrow" GraphRef="n33_REACTOME_264618" RelX="-0.03389830508474576" RelY="-1.1612903225806452"/> <Point X="1424.0" Y="192.0" GraphId="e_244_o1_1" GraphRef="e_244_a_o"/> </Graphics> </Line> <Line GraphId="e_244_o2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1393.0" Y="209.0" GraphId="e_244_o2_0" ArrowHead="Arrow" GraphRef="n22_REACTOME_352022" RelX="0.7301587301587301" RelY="-1.1612903225806452"/> <Point X="1424.0" Y="192.0" GraphId="e_244_o2_1" GraphRef="e_244_a_o"/> </Graphics> </Line> <Line GraphId="e_244_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1403.0" Y="161.0" GraphId="e_244_c__0_0" GraphRef="n31_REACTOME_429572" RelX="1.2121212121212122" RelY="0.0"/> <Point X="1424.0" Y="161.0" GraphId="e_244_c__0_1" GraphRef="e_244_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_245_REACTOME_442661"> <Comment Source="WikiPathways-description">Magnesium (Mg2+) is an abundant cation that is important for many intracellular biochemical functions, especially as a cofactor for ATP. Intracellular Mg2+ concentrations must be finely regulated and recently, transporters for this cation have been elucidated. The human genes SLC41A1 and SLC41A2 encode magnesium transport proteins 1 and 2 respectively (MagT1 and MagT2). They both mediate the uptake of Mg2+ into cells (Goytain A and Quamme GA, 2005; Sahni J et al, 2007). A third human gene, SLC41A3, is also thought to encode a MagT protein but has not been characterized yet.</Comment> <BiopaxRef>lit_442663</BiopaxRef> <BiopaxRef>lit_442668</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1260.0" Y="102.0" GraphId="e_245_0" GraphRef="n30_REACTOME_114632" RelX="-0.024691358024691357" RelY="1.2258064516129032"/> <Point X="1260.0" Y="158.0" GraphId="e_245_1"/> <Point X="1260.0" Y="209.0" GraphId="e_245_2" GraphRef="n5_REACTOME_29926" RelX="-0.024691358024691357" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.5233644859813084" GraphId="e_245_a_p"/> </Graphics> </Line> <Line GraphId="e_245_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1234.0" Y="159.0" GraphId="e_245_c__0_0" GraphRef="n13_REACTOME_442654" RelX="1.1272727272727272" RelY="-0.08695652173913043"/> <Point X="1260.0" Y="158.0" GraphId="e_245_c__0_1" GraphRef="e_245_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_246_REACTOME_444433"> <Comment Source="WikiPathways-description">CTL1 (Wille S et al, 2001) broadly expressed on leukocytes and endothelial cells. CTL2 (Nair TS et al, 2004) highly expressed in human inner ear and is the target of antibody-induced hearing loss.</Comment> <BiopaxRef>lit_444435</BiopaxRef> <BiopaxRef>lit_444455</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1820.0" Y="104.0" GraphId="e_246_0" GraphRef="n34_REACTOME_264638" RelX="-0.03389830508474576" RelY="1.2258064516129032"/> <Point X="1820.0" Y="159.0" GraphId="e_246_1"/> <Point X="1820.0" Y="214.0" GraphId="e_246_2" GraphRef="n35_REACTOME_264618" RelX="-0.03389830508474576" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.5" GraphId="e_246_a_p"/> </Graphics> </Line> <Line GraphId="e_246_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1798.0" Y="160.0" GraphId="e_246_c__0_0" GraphRef="n12_REACTOME_444452" RelX="1.1428571428571428" RelY="-0.08695652173913043"/> <Point X="1820.0" Y="159.0" GraphId="e_246_c__0_1" GraphRef="e_246_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_247_REACTOME_189242"> <Comment Source="WikiPathways-description">The reversible facilitated diffusion of fructose, galactose, and glucose from the cytosol to the extracellular space is mediated by the GLUT2 transporter in the plasma membrane. In the epithelial cells of the small intestine, the basolateral localization of GLUT2 (Thorens et al. 1990) enables hexose sugars derived from the diet and taken up by the action of the SGLT1 and GLUT5 transporters to be released into the circulation. The specificity of the GLUT2 transporter has been established directly through biochemical assays of purified recombinant proteins (Colville et al. 1993; Wu et al. 1998) and indirectly through studies of patients deficient in GLUT2 transporter protein (Santer et al. 1997).</Comment> <BiopaxRef>lit_189239</BiopaxRef> <BiopaxRef>lit_189220</BiopaxRef> <BiopaxRef>lit_189235</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="785.0" Y="205.0" GraphId="e_247_0" GraphRef="n47_REACTOME_189246" RelX="-0.015873015873015872" RelY="-1.1304347826086956"/> <Point X="785.0" Y="158.0" GraphId="e_247_1"/> <Point X="787.0" Y="93.0" GraphId="e_247_2" GraphRef="n45_REACTOME_189219" RelX="-0.015873015873015872" RelY="1.1304347826086956" ArrowHead="Arrow"/> <Anchor Position="0.41952762956591705" GraphId="e_247_a_p"/> </Graphics> </Line> <Line GraphId="e_247_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="761.0" Y="158.0" GraphId="e_247_c__0_0" GraphRef="n43_REACTOME_70422" RelX="1.0625" RelY="-0.08695652173913043"/> <Point X="785.0" Y="158.0" GraphId="e_247_c__0_1" GraphRef="e_247_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_248_REACTOME_428825"> <Comment Source="WikiPathways-description">The class I facilitative glucose transporters contain GLUT1-4. As well as glucose, these proteins can transport other hexoses such as fructose, galactose and glucosamine. GLUT1 was cloned from a HepG2 cell line (Mueckler M et al, 1985). GLUT1 is expressed by SLC2A1 mainly in brain and erythrocytes but is also expressed at lower levels in many other tissues containing endothelial and epithelial barriers. Defects in SLC2A1 are the cause of autosomal dominant GLUT1 deficiency syndrome which results in impaired glucose transport across the brain tissue barrier and is characterized by infantile seizures, delayed development and acquired microcephaly (Klepper J et al, 1999).&lt;br&gt;&lt;br&gt;GLUT2 is expressed by SLC2A2 and is a low affinity glucose transporter (Fukumoto H et al, 1988). It is expressed mainly in the kidney, liver and pancreatic beta-cells. In beta-cells, it functions as a glucose-sensor for insulin secretion and in the liver, it allows for bi-directional glucose transport. In this reaction, it is shown to mediate the influx of glucose. In the next reaction, it is shown to be mediating efflux of glucose. Defects in SLC2A2 are the cause of Fanconi-Bickel syndrome (FBS). It is characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose (Burwinkel B et al, 1999).&lt;br&gt;&lt;br&gt;SLC2A3 encodes GLUT3 which is mainly expressed in the brain but also in a wide range of tissues. If has a high affinity for glucose and can also transport other sugars (Kayano T et al, 1988). GLUT4, encoded by SLC2A4, is an insulin-responsive glucose transporter found in heart, skeletal muscle, brain and adipose tissue. Due to its sensitivity to insulin, it may play a role in diabetes. In a non-insulin condition, GLUT4 is localized in intracellular GLUT4-containing vesicles. On insulin stimulation, GLUT4 translocates to the plasma membrane where it can increase glucose transport 10-20-fold (Fukumoto H et al, 1989). Defects in SLC2A4 may be a cause of non-insulin-dependent diabetes mellitus (NIDDM) (Kusari J et al, 1991; Choi WH et al, 1991).</Comment> <BiopaxRef>lit_428784</BiopaxRef> <BiopaxRef>lit_428791</BiopaxRef> <BiopaxRef>lit_428816</BiopaxRef> <BiopaxRef>lit_428815</BiopaxRef> <BiopaxRef>lit_428788</BiopaxRef> <BiopaxRef>lit_70388</BiopaxRef> <BiopaxRef>lit_428811</BiopaxRef> <BiopaxRef>lit_428777</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1009.0" Y="113.0" GraphId="e_248_0" GraphRef="n49_REACTOME_70115" RelX="0.1111111111111111" RelY="1.2258064516129032"/> <Point X="1031.0" Y="162.0" GraphId="e_248_1"/> <Point X="1012.0" Y="218.0" GraphId="e_248_2" GraphRef="n46_REACTOME_70113" RelX="0.09259259259259259" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.4759709549130731" GraphId="e_248_a_p"/> </Graphics> </Line> <Line GraphId="e_248_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1051.0" Y="161.0" GraphId="e_248_c__0_0" GraphRef="n48_REACTOME_428789" RelX="-1.0561797752808988" RelY="0.0"/> <Point X="1031.0" Y="162.0" GraphId="e_248_c__0_1" GraphRef="e_248_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_249_REACTOME_429094"> <Comment Source="WikiPathways-description">Class III facilitative transporters consist of five members; GLUT6, 8, 10, 12 and HMIT (a H+/myo-inositol transporter). They possess a characteristic glycosylation site on loop 9 (found in loop 1 of classes I and II transporters).&lt;br&gt;&lt;br&gt;Four class III facilitative transporters can transport glucose. SLC2A6 encodes GLUT6, expressed mainly in brain, spleen and leucocytes (Doege H et al, 2000a). In literature, this protein is incorrectly described as GLUT9. SLC2A8 encodes GLUT8 and is expressed in brain, testis and adipose tissue (Doege H et al, 2000b). SLC2A10 (located in the Type 2 diabetes-linked region of human chromosome 20q12-13.1) encodes GLUT10, a transporter with high affinity for glucose (McVie-Wylie AJ et al, 2001) . GLUT10 is highly expressed in liver and pancreas but is present in most tissues in lower levels. Defects in SLC2A10 are the cause of arterial tortuosity syndrome (ATS), an autosomal recessive disorder characterized by tortuosity and elongation of major arteries, often resulting in death at a young age (Coucke PJ et al, 2006). SLC2A12 encodes GLUT12, which is highly expressed in skeletal muscle, heart and prostate, with lower levels in brain, placenta and kidney. It was originally cloned from the human breast cancer cell line MCF-7 (Rogers S et al, 2002).</Comment> <BiopaxRef>lit_429063</BiopaxRef> <BiopaxRef>lit_429043</BiopaxRef> <BiopaxRef>lit_429132</BiopaxRef> <BiopaxRef>lit_429099</BiopaxRef> <BiopaxRef>lit_429134</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="997.0" Y="113.0" GraphId="e_249_0" GraphRef="n49_REACTOME_70115" RelX="-0.1111111111111111" RelY="1.2258064516129032"/> <Point X="981.0" Y="159.0" GraphId="e_249_1"/> <Point X="1001.0" Y="218.0" GraphId="e_249_2" GraphRef="n46_REACTOME_70113" RelX="-0.1111111111111111" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.43876403095267985" GraphId="e_249_a_p"/> </Graphics> </Line> <Line GraphId="e_249_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="953.0" Y="159.0" GraphId="e_249_c__0_0" GraphRef="n44_REACTOME_429047" RelX="1.0769230769230769" RelY="-0.08695652173913043"/> <Point X="981.0" Y="159.0" GraphId="e_249_c__0_1" GraphRef="e_249_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_250_REACTOME_428779"> <Comment Source="WikiPathways-description">SLC2A7 encodes GLUT7, a class II facilitative glucose transporter which was cloned from a human intestinal cDNA library (Li Q et al, 2004). It has a high affinity for glucose and fructose uptake. GLUT7 is found predominantly in the small intestine, colon, testis and prostate.&lt;br&gt;&lt;br&gt;SLC2A11 encodes GLUT11 (Doege H et al, 2001), another member of the class II facilitative glucose transporters. It has the highest similarity with GLUT5 and in humans, three isoforms are expressed (GLUT11A-C) (Sasaki T et al, 2001). Human GLUT11 has been shown to transport glucose and fructose but not galactose when expressed in Xenopus oocytes ( Scheepers A et al, 2005).</Comment> <BiopaxRef>lit_428803</BiopaxRef> <BiopaxRef>lit_429104</BiopaxRef> <BiopaxRef>lit_429042</BiopaxRef> <BiopaxRef>lit_429061</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="599.0" Y="110.0" GraphId="e_250_0" GraphRef="n50_REACTOME_428819" RelX="-0.015151515151515152" RelY="1.1304347826086956"/> <Point X="599.0" Y="160.0" GraphId="e_250_1"/> <Point X="599.0" Y="211.0" GraphId="e_250_2" GraphRef="n58_REACTOME_428802" RelX="-0.015151515151515152" RelY="-1.1304347826086956" ArrowHead="Arrow"/> <Anchor Position="0.49504950495049505" GraphId="e_250_a_p"/> </Graphics> </Line> <Line GraphId="e_250_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="573.0" Y="161.0" GraphId="e_250_c__0_0" GraphRef="n55_REACTOME_429107" RelX="1.09375" RelY="-0.17391304347826086"/> <Point X="599.0" Y="160.0" GraphId="e_250_c__0_1" GraphRef="e_250_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_251_REACTOME_429036"> <Comment Source="WikiPathways-description">The human SLC2A9 gene encodes two isoforms of class II facilitative glucose transporter 9; GLUT9 (Phay JE et al, 2000) and GLUT9DeltaN (Augustin R et al, 2004). GLUT9 is expressed mainly in kidney (proximal tubules of epithelial cells) and liver while GLUT9DeltaN is expressed mainly in kidney and placenta. As well as mediating the uptake of fructose and glucose (at a low rate), GLUT9 can also mediate the tranpsort of urate (uric acid), the end product of purine metabolism in humans and great apes (Vitart V et al, 2008). Mutations in SLC2A9 influence serum urate concentrations with excess serum accumulation of urate leading to the development of gout (Vitart V et al, 2008).</Comment> <BiopaxRef>lit_429057</BiopaxRef> <BiopaxRef>lit_429062</BiopaxRef> <BiopaxRef>lit_429097</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3681.0" Y="108.0" GraphId="e_251_0" GraphRef="n54_REACTOME_429078" RelX="0.0" RelY="1.1304347826086956"/> <Point X="3681.0" Y="161.0" GraphId="e_251_1"/> <Point X="3681.0" Y="235.0" GraphId="e_251_2" GraphRef="n51_REACTOME_429148" RelX="-0.014705882352941176" RelY="-1.1304347826086956" ArrowHead="Arrow"/> <Anchor Position="0.41732283464566927" GraphId="e_251_a_p"/> </Graphics> </Line> <Line GraphId="e_251_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3655.0" Y="158.0" GraphId="e_251_c__0_0" GraphRef="n52_REACTOME_429065" RelX="1.148936170212766" RelY="0.08695652173913043"/> <Point X="3681.0" Y="161.0" GraphId="e_251_c__0_1" GraphRef="e_251_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_252_REACTOME_189222"> <Comment Source="WikiPathways-description">The reversible transport of extracellular fructose into the cytosol is mediated by GLUT5. In the small intestine, GLUT5 is localized on the lumenal surfaces of enterocytes (Davidson et al. 1992) and thus mediates the uptake of dietary fructose, which can be released into the circulation in a separate transport step mediated by basolaterally localized GLUT2. The specificity of GLUT5 has been worked out by studying sugar transport in Xenopus oocytes expressing recombinant human GLUT5 protein (Burant et al. 1992).</Comment> <BiopaxRef>lit_189217</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="455.0" Y="105.0" GraphId="e_252_0" GraphRef="n57_REACTOME_189049" RelX="0.0" RelY="1.2258064516129032"/> <Point X="455.0" Y="158.0" GraphId="e_252_1"/> <Point X="455.0" Y="214.0" GraphId="e_252_2" GraphRef="n56_REACTOME_29532" RelX="0.0" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.48623853211009177" GraphId="e_252_a_p"/> </Graphics> </Line> <Line GraphId="e_252_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="431.0" Y="159.0" GraphId="e_252_c__0_0" GraphRef="n53_REACTOME_189202" RelX="1.148936170212766" RelY="-0.08695652173913043"/> <Point X="455.0" Y="158.0" GraphId="e_252_c__0_1" GraphRef="e_252_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_253_REACTOME_429613"> <Comment Source="WikiPathways-description">The human gene SLC5A2 encodes a sodium-dependent glucose transporter, SGLT2 (Wells RG et al, 1992). SGLT2 is expressed in many tissues but primarily in the kidney, specifically the renal proximal tubules (S1 and S2 segments).It is a low affinity, high capacity transporter of glucose across the apical membrane, with co-transport of Na+ ions in a 1:1 ratio. Unlike SGLT1, it doesn't transport galactose. SGLT2 is the main transporter of glucose in the kidney, responsible for approximately 98% of glucose reabsorption (reaminder by SGLT1). Defects in SLC5A2 are the cause of renal glucosuria (GLYS1), an autosomal recessive renal tubular disorder (Calado J et al, 2004).</Comment> <BiopaxRef>lit_429617</BiopaxRef> <BiopaxRef>lit_429604</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3037.0" Y="106.0" GraphId="e_253_0"/> <Point X="3038.0" Y="163.0" GraphId="e_253_1"/> <Point X="3037.0" Y="203.0" GraphId="e_253_2"/> <Anchor Position="0.0" GraphId="e_253_a_i"/> <Anchor Position="0.5875904496491884" GraphId="e_253_a_p"/> <Anchor Position="1.0" GraphId="e_253_a_o"/> </Graphics> </Line> <Line GraphId="e_253_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3038.0" Y="80.0" GraphId="e_253_i0_0" GraphRef="n66_REACTOME_70115" RelX="-0.037037037037037035" RelY="1.2258064516129032"/> <Point X="3037.0" Y="106.0" GraphId="e_253_i0_1" GraphRef="e_253_a_i"/> </Graphics> </Line> <Line GraphId="e_253_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3070.0" Y="107.0" GraphId="e_253_i1_0" GraphRef="n68_REACTOME_74113" RelX="-1.0769230769230769" RelY="-0.12903225806451613"/> <Point X="3037.0" Y="106.0" GraphId="e_253_i1_1" GraphRef="e_253_a_i"/> </Graphics> </Line> <Line GraphId="e_253_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3037.0" Y="264.0" GraphId="e_253_o0_0" ArrowHead="Arrow" GraphRef="n67_REACTOME_70113" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="3037.0" Y="203.0" GraphId="e_253_o0_1" GraphRef="e_253_a_o"/> </Graphics> </Line> <Line GraphId="e_253_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3085.0" Y="203.0" GraphId="e_253_o1_0" ArrowHead="Arrow" GraphRef="n73_REACTOME_83910" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="3037.0" Y="203.0" GraphId="e_253_o1_1" GraphRef="e_253_a_o"/> </Graphics> </Line> <Line GraphId="e_253_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3015.0" Y="160.0" GraphId="e_253_c__0_0" GraphRef="n64_REACTOME_429568" RelX="1.1304347826086956" RelY="0.08695652173913043"/> <Point X="3038.0" Y="163.0" GraphId="e_253_c__0_1" GraphRef="e_253_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_254_REACTOME_189208"> <Comment Source="WikiPathways-description">The transport of extracellular glucose and galactose into the cytosol, coupled to the uptake of two sodium ions for each hexose transported is mediated by SGLT1. In the small intestine, SGLT1 is localized on the lumenal surfaces of enterocytes and thus mediates the uptake of dietary glucose and galactose, which can be released into the circulation in a separate transport step mediated by basolaterally localized GLUT2 (Wright et al. 2004). The specificity of SGLT1 has been worked out by studying sugar transport in plasma membrane vesicles containing recombinant human SGLT1 protein (Quick et al. 2003). Consistent with these in vitro results, children lacking functional SGLT1 protein fail to absord dietary glucose and galactose (Martin et al. 1996).</Comment> <BiopaxRef>lit_189223</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3231.0" Y="113.0" GraphId="e_254_0"/> <Point X="3232.0" Y="162.0" GraphId="e_254_1"/> <Point X="3232.0" Y="205.0" GraphId="e_254_2"/> <Anchor Position="0.0" GraphId="e_254_a_i"/> <Anchor Position="0.5326605247143408" GraphId="e_254_a_p"/> <Anchor Position="1.0" GraphId="e_254_a_o"/> </Graphics> </Line> <Line GraphId="e_254_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3231.0" Y="56.0" GraphId="e_254_i0_0" GraphRef="n60_REACTOME_189227" RelX="0.0" RelY="1.2258064516129032"/> <Point X="3231.0" Y="113.0" GraphId="e_254_i0_1" GraphRef="e_254_a_i"/> </Graphics> </Line> <Line GraphId="e_254_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3278.0" Y="112.0" GraphId="e_254_i1_0" GraphRef="n70_REACTOME_74113" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="3231.0" Y="113.0" GraphId="e_254_i1_1" GraphRef="e_254_a_i"/> </Graphics> </Line> <Line GraphId="e_254_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3232.0" Y="263.0" GraphId="e_254_o0_0" ArrowHead="Arrow" GraphRef="n59_REACTOME_189254" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="3232.0" Y="205.0" GraphId="e_254_o0_1" GraphRef="e_254_a_o"/> </Graphics> </Line> <Line GraphId="e_254_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3286.0" Y="205.0" GraphId="e_254_o1_0" ArrowHead="Arrow" GraphRef="n71_REACTOME_83910" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="3232.0" Y="205.0" GraphId="e_254_o1_1" GraphRef="e_254_a_o"/> </Graphics> </Line> <Line GraphId="e_254_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3205.0" Y="160.0" GraphId="e_254_c__0_0" GraphRef="n61_REACTOME_189243" RelX="1.1304347826086956" RelY="0.08695652173913043"/> <Point X="3232.0" Y="162.0" GraphId="e_254_c__0_1" GraphRef="e_254_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_255_REACTOME_429567"> <Comment Source="WikiPathways-description">The human gene SLC5A9 encodes a low affinity transporter for glucose and mannose (SGLT4). Of the tissues tested, SGLT4 appears to be highly expressed in the kidney and intestine, with lower levels detected in the liver. Human SGLT4 expressed in african green monkey cells exhibited glucose and mannose co-transport with Na+ ions (Tazawa S et al, 2005).</Comment> <BiopaxRef>lit_429653</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3487.0" Y="111.0" GraphId="e_255_0"/> <Point X="3487.0" Y="161.0" GraphId="e_255_1"/> <Point X="3487.0" Y="210.0" GraphId="e_255_2"/> <Anchor Position="0.0" GraphId="e_255_a_i"/> <Anchor Position="0.5050505050505051" GraphId="e_255_a_p"/> <Anchor Position="1.0" GraphId="e_255_a_o"/> </Graphics> </Line> <Line GraphId="e_255_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3487.0" Y="77.0" GraphId="e_255_i0_0" GraphRef="n63_REACTOME_429620" RelX="0.0" RelY="1.1304347826086956"/> <Point X="3487.0" Y="111.0" GraphId="e_255_i0_1" GraphRef="e_255_a_i"/> </Graphics> </Line> <Line GraphId="e_255_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3526.0" Y="110.0" GraphId="e_255_i1_0" GraphRef="n69_REACTOME_74113" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="3487.0" Y="111.0" GraphId="e_255_i1_1" GraphRef="e_255_a_i"/> </Graphics> </Line> <Line GraphId="e_255_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3487.0" Y="260.0" GraphId="e_255_o0_0" ArrowHead="Arrow" GraphRef="n65_REACTOME_429628" RelX="-0.015151515151515152" RelY="-1.1304347826086956"/> <Point X="3487.0" Y="210.0" GraphId="e_255_o0_1" GraphRef="e_255_a_o"/> </Graphics> </Line> <Line GraphId="e_255_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3529.0" Y="210.0" GraphId="e_255_o1_0" ArrowHead="Arrow" GraphRef="n72_REACTOME_83910" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="3487.0" Y="210.0" GraphId="e_255_o1_1" GraphRef="e_255_a_o"/> </Graphics> </Line> <Line GraphId="e_255_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3460.0" Y="161.0" GraphId="e_255_c__0_0" GraphRef="n62_REACTOME_429650" RelX="1.1304347826086956" RelY="-0.08695652173913043"/> <Point X="3487.0" Y="161.0" GraphId="e_255_c__0_1" GraphRef="e_255_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_256_REACTOME_429101"> <Comment Source="WikiPathways-description">SLC2A13 encodes a H+/myo-inositol co-transporter, HMIT (Uldry M et al, 2001) which is abundantly expressed in the brain. A proton is co-transported with myo-inositol uptake into cells. No glucose transport function has been detected to date.</Comment> <BiopaxRef>lit_429051</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2618.0" Y="889.0" GraphId="e_256_0"/> <Point X="2618.0" Y="827.0" GraphId="e_256_1"/> <Point X="2618.0" Y="761.0" GraphId="e_256_2"/> <Anchor Position="0.0" GraphId="e_256_a_i"/> <Anchor Position="0.484375" GraphId="e_256_a_p"/> <Anchor Position="1.0" GraphId="e_256_a_o"/> </Graphics> </Line> <Line GraphId="e_256_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2664.0" Y="889.0" GraphId="e_256_i0_0" GraphRef="n86_REACTOME_351626" RelX="-1.1875" RelY="0.0"/> <Point X="2618.0" Y="889.0" GraphId="e_256_i0_1" GraphRef="e_256_a_i"/> </Graphics> </Line> <Line GraphId="e_256_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2618.0" Y="947.0" GraphId="e_256_i1_0" GraphRef="n87_REACTOME_429130" RelX="-0.03571428571428571" RelY="-1.1612903225806452"/> <Point X="2618.0" Y="889.0" GraphId="e_256_i1_1" GraphRef="e_256_a_i"/> </Graphics> </Line> <Line GraphId="e_256_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2669.0" Y="761.0" GraphId="e_256_o0_0" ArrowHead="Arrow" GraphRef="n85_REACTOME_70106" RelX="-1.1875" RelY="-0.06451612903225806"/> <Point X="2618.0" Y="761.0" GraphId="e_256_o0_1" GraphRef="e_256_a_o"/> </Graphics> </Line> <Line GraphId="e_256_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2618.0" Y="715.0" GraphId="e_256_o1_0" ArrowHead="Arrow" GraphRef="n88_REACTOME_426910" RelX="0.0" RelY="1.2258064516129032"/> <Point X="2618.0" Y="761.0" GraphId="e_256_o1_1" GraphRef="e_256_a_o"/> </Graphics> </Line> <Line GraphId="e_256_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="2597.0" Y="825.0" GraphId="e_256_c__0_0" GraphRef="n76_REACTOME_429102" RelX="1.0598290598290598" RelY="0.10526315789473684"/> <Point X="2618.0" Y="827.0" GraphId="e_256_c__0_1" GraphRef="e_256_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_257_REACTOME_429663"> <Comment Source="WikiPathways-description">The human SLC5A3 gene encodes a Na+/myo-inositol transporter, SMIT (Berry GT et al, 1995). SMIT functions in cellular osmoregulation and is expressed in many human tissues including skeletal muscle, brain, kidney, and placenta. It transports myo-inositol together with two Na+ ions. SMIT is also thought to act as a glucose sensor that generates an intracellular glucose signal.</Comment> <BiopaxRef>lit_429654</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2846.0" Y="117.0" GraphId="e_257_0"/> <Point X="2846.0" Y="160.0" GraphId="e_257_1"/> <Point X="2846.0" Y="214.0" GraphId="e_257_2"/> <Anchor Position="0.0" GraphId="e_257_a_i"/> <Anchor Position="0.44329896907216493" GraphId="e_257_a_p"/> <Anchor Position="1.0" GraphId="e_257_a_o"/> </Graphics> </Line> <Line GraphId="e_257_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2846.0" Y="72.0" GraphId="e_257_i0_0" GraphRef="n77_REACTOME_429130" RelX="0.0" RelY="1.2258064516129032"/> <Point X="2846.0" Y="117.0" GraphId="e_257_i0_1" GraphRef="e_257_a_i"/> </Graphics> </Line> <Line GraphId="e_257_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2889.0" Y="117.0" GraphId="e_257_i1_0" GraphRef="n83_REACTOME_74113" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="2846.0" Y="117.0" GraphId="e_257_i1_1" GraphRef="e_257_a_i"/> </Graphics> </Line> <Line GraphId="e_257_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2846.0" Y="259.0" GraphId="e_257_o0_0" ArrowHead="Arrow" GraphRef="n78_REACTOME_426910" RelX="-0.03571428571428571" RelY="-1.1612903225806452"/> <Point X="2846.0" Y="214.0" GraphId="e_257_o0_1" GraphRef="e_257_a_o"/> </Graphics> </Line> <Line GraphId="e_257_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2901.0" Y="214.0" GraphId="e_257_o1_0" ArrowHead="Arrow" GraphRef="n82_REACTOME_83910" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="2846.0" Y="214.0" GraphId="e_257_o1_1" GraphRef="e_257_a_o"/> </Graphics> </Line> <Line GraphId="e_257_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="2821.0" Y="159.0" GraphId="e_257_c__0_0" GraphRef="n80_REACTOME_429592" RelX="1.2" RelY="0.0"/> <Point X="2846.0" Y="160.0" GraphId="e_257_c__0_1" GraphRef="e_257_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_258_REACTOME_429571"> <Comment Source="WikiPathways-description">The human SLC5A11 gene encodes a high affinity myo-inositol transporter (SMIT2, SGLT6) (Ostlund RE et al, 1996; Roll P et al, 2002). It can transport myo-inositol and D-chiro-inositol, together with two Na+ ions. It was thought SGLT6 could transport glucose but there is no evidence for this so far (Lin X et al, 2009).</Comment> <BiopaxRef>lit_429625</BiopaxRef> <BiopaxRef>lit_429597</BiopaxRef> <BiopaxRef>lit_429636</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2337.0" Y="881.0" GraphId="e_258_0"/> <Point X="2337.0" Y="827.0" GraphId="e_258_1"/> <Point X="2336.0" Y="757.0" GraphId="e_258_2"/> <Anchor Position="0.0" GraphId="e_258_a_i"/> <Anchor Position="0.4354587882158296" GraphId="e_258_a_p"/> <Anchor Position="1.0" GraphId="e_258_a_o"/> </Graphics> </Line> <Line GraphId="e_258_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2337.0" Y="934.0" GraphId="e_258_i0_0" GraphRef="n79_REACTOME_429652" RelX="0.0" RelY="-1.1304347826086956"/> <Point X="2337.0" Y="881.0" GraphId="e_258_i0_1" GraphRef="e_258_a_i"/> </Graphics> </Line> <Line GraphId="e_258_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2389.0" Y="881.0" GraphId="e_258_i1_0" GraphRef="n84_REACTOME_74113" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="2337.0" Y="881.0" GraphId="e_258_i1_1" GraphRef="e_258_a_i"/> </Graphics> </Line> <Line GraphId="e_258_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2336.0" Y="698.0" GraphId="e_258_o0_0" ArrowHead="Arrow" GraphRef="n75_REACTOME_429648" RelX="0.0" RelY="1.1304347826086956"/> <Point X="2336.0" Y="757.0" GraphId="e_258_o0_1" GraphRef="e_258_a_o"/> </Graphics> </Line> <Line GraphId="e_258_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2390.0" Y="757.0" GraphId="e_258_o1_0" ArrowHead="Arrow" GraphRef="n81_REACTOME_83910" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="2336.0" Y="757.0" GraphId="e_258_o1_1" GraphRef="e_258_a_o"/> </Graphics> </Line> <Line GraphId="e_258_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="2310.0" Y="826.0" GraphId="e_258_c__0_0" GraphRef="n74_REACTOME_429589" RelX="1.1428571428571428" RelY="0.0"/> <Point X="2337.0" Y="827.0" GraphId="e_258_c__0_1" GraphRef="e_258_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_259_REACTOME_433104"> <Comment Source="WikiPathways-description">The human SLC13A5 gene encodes a sodium-coupled citrate transporter, NACT. This gene is expressed mainly in the liver, with lower levels in brain and testis. NACT has a preference for trivalent citrate (Inoue K et al, 2002).</Comment> <BiopaxRef>lit_433112</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1907.0" Y="881.0" GraphId="e_259_0"/> <Point X="1907.0" Y="829.0" GraphId="e_259_1"/> <Point X="1907.0" Y="754.0" GraphId="e_259_2"/> <Anchor Position="0.0" GraphId="e_259_a_i"/> <Anchor Position="0.4094488188976378" GraphId="e_259_a_p"/> <Anchor Position="1.0" GraphId="e_259_a_o"/> </Graphics> </Line> <Line GraphId="e_259_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1906.0" Y="935.0" GraphId="e_259_i0_0" GraphRef="n99_REACTOME_433138" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="1907.0" Y="881.0" GraphId="e_259_i0_1" GraphRef="e_259_a_i"/> </Graphics> </Line> <Line GraphId="e_259_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1935.0" Y="880.0" GraphId="e_259_i1_0" GraphRef="n108_REACTOME_74113" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="1907.0" Y="881.0" GraphId="e_259_i1_1" GraphRef="e_259_a_i"/> </Graphics> </Line> <Line GraphId="e_259_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1951.0" Y="753.0" GraphId="e_259_o0_0" ArrowHead="Arrow" GraphRef="n96_REACTOME_76190" RelX="-1.1153846153846154" RelY="0.0"/> <Point X="1907.0" Y="754.0" GraphId="e_259_o0_1" GraphRef="e_259_a_o"/> </Graphics> </Line> <Line GraphId="e_259_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1907.0" Y="710.0" GraphId="e_259_o1_0" ArrowHead="Arrow" GraphRef="n102_REACTOME_83910" RelX="0.0" RelY="1.2258064516129032"/> <Point X="1907.0" Y="754.0" GraphId="e_259_o1_1" GraphRef="e_259_a_o"/> </Graphics> </Line> <Line GraphId="e_259_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1880.0" Y="827.0" GraphId="e_259_c__0_0" GraphRef="n100_REACTOME_433135" RelX="1.0588235294117647" RelY="0.15789473684210525"/> <Point X="1907.0" Y="829.0" GraphId="e_259_c__0_1" GraphRef="e_259_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_260_REACTOME_433099"> <Comment Source="WikiPathways-description">The human gene SLC13A4 encodes a sodium/sulphate co-transporter NaS2 (Girard JP et al, 1999). NaS2 is highly expressed in placenta and testis, mainly in high endothelial venules. Kinetic experiments suggest two sodium ions co-transported for every sulphate ion (Markovich D et al, 2005).</Comment> <BiopaxRef>lit_433108</BiopaxRef> <BiopaxRef>lit_433122</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1464.0" Y="899.0" GraphId="e_260_0"/> <Point X="1464.0" Y="830.0" GraphId="e_260_1"/> <Point X="1464.0" Y="744.0" GraphId="e_260_2"/> <Anchor Position="0.0" GraphId="e_260_a_i"/> <Anchor Position="0.44516129032258067" GraphId="e_260_a_p"/> <Anchor Position="1.0" GraphId="e_260_a_o"/> </Graphics> </Line> <Line GraphId="e_260_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1393.0" Y="957.0" GraphId="e_260_i0_0" GraphRef="n90_REACTOME_427648" RelX="0.3177570093457944" RelY="-1.1612903225806452"/> <Point X="1464.0" Y="899.0" GraphId="e_260_i0_1" GraphRef="e_260_a_i"/> </Graphics> </Line> <Line GraphId="e_260_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1416.0" Y="899.0" GraphId="e_260_i1_0" GraphRef="n107_REACTOME_74113" RelX="1.0769230769230769" RelY="0.0"/> <Point X="1464.0" Y="899.0" GraphId="e_260_i1_1" GraphRef="e_260_a_i"/> </Graphics> </Line> <Line GraphId="e_260_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1394.0" Y="700.0" GraphId="e_260_o0_0" ArrowHead="Arrow" GraphRef="n89_REACTOME_174375" RelX="0.411214953271028" RelY="1.2258064516129032"/> <Point X="1464.0" Y="744.0" GraphId="e_260_o0_1" GraphRef="e_260_a_o"/> </Graphics> </Line> <Line GraphId="e_260_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1416.0" Y="745.0" GraphId="e_260_o1_0" ArrowHead="Arrow" GraphRef="n103_REACTOME_83910" RelX="1.0769230769230769" RelY="-0.12903225806451613"/> <Point X="1464.0" Y="744.0" GraphId="e_260_o1_1" GraphRef="e_260_a_o"/> </Graphics> </Line> <Line GraphId="e_260_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1483.0" Y="829.0" GraphId="e_260_c__0_0" GraphRef="n94_REACTOME_433098" RelX="-1.1282051282051282" RelY="0.0"/> <Point X="1464.0" Y="830.0" GraphId="e_260_c__0_1" GraphRef="e_260_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_261_REACTOME_433101"> <Comment Source="WikiPathways-description">Mammalian sodium/dicarboxylate cotransporters (transport succinate and other Krebs cycle intermediates) fall into two categories based on their substrate affinity. The human gene SLC13A3 encodes a high-affinity sodium/dicarboxlate co-transporter, NaDC3. NaDC3 is expressed in the basolateral membrane of renal proximal tubular epithelial cells, sinusoidal membrane of hepatocytes, and brain synaptosomes. Kinetic studies in human retinal pigment epithelial (HRPE) cells suggest three sodium ions co-transported with every divalent succinate (Wang H et al, 2000).</Comment> <BiopaxRef>lit_433116</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2122.0" Y="878.0" GraphId="e_261_0"/> <Point X="2122.0" Y="829.0" GraphId="e_261_1"/> <Point X="2122.0" Y="776.0" GraphId="e_261_2"/> <Anchor Position="0.0" GraphId="e_261_a_i"/> <Anchor Position="0.4803921568627451" GraphId="e_261_a_p"/> <Anchor Position="1.0" GraphId="e_261_a_o"/> </Graphics> </Line> <Line GraphId="e_261_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2122.0" Y="931.0" GraphId="e_261_i0_0" GraphRef="n91_REACTOME_433123" RelX="-0.02857142857142857" RelY="-1.1612903225806452"/> <Point X="2122.0" Y="878.0" GraphId="e_261_i0_1" GraphRef="e_261_a_i"/> </Graphics> </Line> <Line GraphId="e_261_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2177.0" Y="876.0" GraphId="e_261_i1_0" GraphRef="n106_REACTOME_74113" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="2122.0" Y="878.0" GraphId="e_261_i1_1" GraphRef="e_261_a_i"/> </Graphics> </Line> <Line GraphId="e_261_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2122.0" Y="731.0" GraphId="e_261_o0_0" ArrowHead="Arrow" GraphRef="n98_REACTOME_29434" RelX="0.0" RelY="1.2258064516129032"/> <Point X="2122.0" Y="776.0" GraphId="e_261_o0_1" GraphRef="e_261_a_o"/> </Graphics> </Line> <Line GraphId="e_261_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2183.0" Y="776.0" GraphId="e_261_o1_0" ArrowHead="Arrow" GraphRef="n105_REACTOME_83910" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="2122.0" Y="776.0" GraphId="e_261_o1_1" GraphRef="e_261_a_o"/> </Graphics> </Line> <Line GraphId="e_261_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="2099.0" Y="829.0" GraphId="e_261_c__0_0" GraphRef="n101_REACTOME_433095" RelX="1.1428571428571428" RelY="0.0"/> <Point X="2122.0" Y="829.0" GraphId="e_261_c__0_1" GraphRef="e_261_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_262_REACTOME_433131"> <Comment Source="WikiPathways-description">Mammalian sodium/dicarboxylate cotransporters (transport succinate and other Krebs cycle intermediates) fall into two categories based on their substrate affinity. The human gene SLC13A2 encodes a low-affinity sodium/dicarboxlate co-transporter, NaDC1. NaDC1 is highly expressed in the brush-border membranes of kidney and intestinal cells and reabsorbs Krebs cycle intermediates, such as succinate and citrate, from the glomerular filtrate (Pajor AM, 1996).</Comment> <BiopaxRef>lit_433096</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1627.0" Y="888.0" GraphId="e_262_0"/> <Point X="1627.0" Y="824.0" GraphId="e_262_1"/> <Point X="1626.0" Y="745.0" GraphId="e_262_2"/> <Anchor Position="0.0" GraphId="e_262_a_i"/> <Anchor Position="0.4475326407579413" GraphId="e_262_a_p"/> <Anchor Position="1.0" GraphId="e_262_a_o"/> </Graphics> </Line> <Line GraphId="e_262_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1627.0" Y="941.0" GraphId="e_262_i0_0" GraphRef="n97_REACTOME_433111" RelX="0.0" RelY="-1.1304347826086956"/> <Point X="1627.0" Y="888.0" GraphId="e_262_i0_1" GraphRef="e_262_a_i"/> </Graphics> </Line> <Line GraphId="e_262_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1660.0" Y="888.0" GraphId="e_262_i1_0" GraphRef="n109_REACTOME_74113" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="1627.0" Y="888.0" GraphId="e_262_i1_1" GraphRef="e_262_a_i"/> </Graphics> </Line> <Line GraphId="e_262_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1626.0" Y="696.0" GraphId="e_262_o0_0" ArrowHead="Arrow" GraphRef="n95_REACTOME_433124" RelX="-0.014492753623188406" RelY="1.1304347826086956"/> <Point X="1626.0" Y="745.0" GraphId="e_262_o0_1" GraphRef="e_262_a_o"/> </Graphics> </Line> <Line GraphId="e_262_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1665.0" Y="745.0" GraphId="e_262_o1_0" ArrowHead="Arrow" GraphRef="n104_REACTOME_83910" RelX="-1.0769230769230769" RelY="-0.06451612903225806"/> <Point X="1626.0" Y="745.0" GraphId="e_262_o1_1" GraphRef="e_262_a_o"/> </Graphics> </Line> <Line GraphId="e_262_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1601.0" Y="824.0" GraphId="e_262_c__0_0" GraphRef="n93_REACTOME_433093" RelX="1.1428571428571428" RelY="0.0"/> <Point X="1627.0" Y="824.0" GraphId="e_262_c__0_1" GraphRef="e_262_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_263_REACTOME_433114"> <Comment Source="WikiPathways-description">The human gene SLC13A1 encodes a sodium/sulphate co-transporter NaS1 (Lee A et al, 2000). NaS1 is almost exclusively expressed in the kidney and mediates sulphate reabsorption there.</Comment> <BiopaxRef>lit_433113</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1296.0" Y="899.0" GraphId="e_263_0"/> <Point X="1296.0" Y="829.0" GraphId="e_263_1"/> <Point X="1296.0" Y="748.0" GraphId="e_263_2"/> <Anchor Position="0.0" GraphId="e_263_a_i"/> <Anchor Position="0.46357615894039733" GraphId="e_263_a_p"/> <Anchor Position="1.0" GraphId="e_263_a_o"/> </Graphics> </Line> <Line GraphId="e_263_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1359.0" Y="957.0" GraphId="e_263_i0_0" GraphRef="n90_REACTOME_427648" RelX="-0.3177570093457944" RelY="-1.1612903225806452"/> <Point X="1296.0" Y="899.0" GraphId="e_263_i0_1" GraphRef="e_263_a_i"/> </Graphics> </Line> <Line GraphId="e_263_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1332.0" Y="899.0" GraphId="e_263_i1_0" GraphRef="n107_REACTOME_74113" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="1296.0" Y="899.0" GraphId="e_263_i1_1" GraphRef="e_263_a_i"/> </Graphics> </Line> <Line GraphId="e_263_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1354.0" Y="700.0" GraphId="e_263_o0_0" ArrowHead="Arrow" GraphRef="n89_REACTOME_174375" RelX="-0.3364485981308411" RelY="1.2258064516129032"/> <Point X="1296.0" Y="748.0" GraphId="e_263_o0_1" GraphRef="e_263_a_o"/> </Graphics> </Line> <Line GraphId="e_263_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1332.0" Y="747.0" GraphId="e_263_o1_0" ArrowHead="Arrow" GraphRef="n103_REACTOME_83910" RelX="-1.0769230769230769" RelY="0.0"/> <Point X="1296.0" Y="748.0" GraphId="e_263_o1_1" GraphRef="e_263_a_o"/> </Graphics> </Line> <Line GraphId="e_263_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1276.0" Y="826.0" GraphId="e_263_c__0_0" GraphRef="n92_REACTOME_433136" RelX="1.1794871794871795" RelY="0.08695652173913043"/> <Point X="1296.0" Y="829.0" GraphId="e_263_c__0_1" GraphRef="e_263_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_264_REACTOME_433698"> <Comment Source="WikiPathways-description">Four members of the SLC16A gene family encode classical monocarboxylate transporters, MCT1-4. They all function as proton-dependent transporters of monocarboxylic acids such as lactate and pyruvate and ketone bodies such as acetacetate and beta-hydroxybutyrate. These processes are crucial in the regulation of energy metabolism and acid-base homeostasis.&lt;br&gt;&lt;br&gt;SLC16A1 encodes MCT1, a ubiquitiously expressed protein (Garcia CK et al, 1994). Defects in SLC16A1 are the cause of symptomatic deficiency in lactate transport (SDLT), resulting in an acidic intracellular environment and muscle degeneration (Merezhinskaya N et al, 2000). Another defect in SLC16A1 causes exercise-induced hyperinsulinism (EIHI), a dominantly inherited hypoglycemic disorder characterized by inappropriate insulin secretion during anaerobic exercise or on pyruvate load (Otonkoski T et al, 2000). SLC16A7 encodes MCT2, a high affinity pyruvate transporter highly expressed in testis (Lin RY et al, 1998). SLC16A8 encodes MCT3 (Yoon H et al, 1999).&lt;br&gt;&lt;br&gt;Human RPE (retinal pigment epithelial) cells express two proton-coupled monocarboxylate transporters: MCT1 in the apical membrane and MCT3 in the basolateral membrane. This suggested that the coordinated activities of these two transporters could facilitate the transepithelial transport of lactate from the retina to the choroid. (Philip NJ et al, 2003).</Comment> <BiopaxRef>lit_433681</BiopaxRef> <BiopaxRef>lit_373885</BiopaxRef> <BiopaxRef>lit_373894</BiopaxRef> <BiopaxRef>lit_433703</BiopaxRef> <BiopaxRef>lit_433697</BiopaxRef> <BiopaxRef>lit_445737</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="179.0" Y="350.0" GraphId="e_264_0"/> <Point X="252.0" Y="350.0" GraphId="e_264_1"/> <Point X="324.0" Y="350.0" GraphId="e_264_2"/> <Anchor Position="0.0" GraphId="e_264_a_i"/> <Anchor Position="0.503448275862069" GraphId="e_264_a_p"/> <Anchor Position="1.0" GraphId="e_264_a_o"/> </Graphics> </Line> <Line GraphId="e_264_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="129.0" Y="351.0" GraphId="e_264_i0_0" GraphRef="n111_REACTOME_433683" RelX="1.0679611650485437" RelY="-0.12903225806451613"/> <Point X="179.0" Y="350.0" GraphId="e_264_i0_1" GraphRef="e_264_a_i"/> </Graphics> </Line> <Line GraphId="e_264_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="179.0" Y="370.0" GraphId="e_264_i1_0" GraphRef="n113_REACTOME_351626" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="179.0" Y="350.0" GraphId="e_264_i1_1" GraphRef="e_264_a_i"/> </Graphics> </Line> <Line GraphId="e_264_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="379.0" Y="351.0" GraphId="e_264_o0_0" ArrowHead="Arrow" GraphRef="n112_REACTOME_433686" RelX="-1.0485436893203883" RelY="-0.06451612903225806"/> <Point X="324.0" Y="350.0" GraphId="e_264_o0_1" GraphRef="e_264_a_o"/> </Graphics> </Line> <Line GraphId="e_264_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="324.0" Y="389.0" GraphId="e_264_o1_0" ArrowHead="Arrow" GraphRef="n114_REACTOME_70106" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="324.0" Y="350.0" GraphId="e_264_o1_1" GraphRef="e_264_a_o"/> </Graphics> </Line> <Line GraphId="e_264_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="251.0" Y="317.0" GraphId="e_264_c__0_0" GraphRef="n110_REACTOME_434162" RelX="0.0" RelY="1.1578947368421053"/> <Point X="252.0" Y="350.0" GraphId="e_264_c__0_1" GraphRef="e_264_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_265_REACTOME_437139"> <Comment Source="WikiPathways-description">Two human genes mediate the transport of zinc into the TGN and they are both localized to the TGN. The human gene SLC30A6 encodes the zinc transporter ZnT6. By Western blot studies, ZnT6 is only found in the brain and lung in human (Huang L et al, 2002).</Comment> <BiopaxRef>lit_437138</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="401.0" Y="537.0" GraphId="e_265_0" GraphRef="n125_REACTOME_29426" RelX="-0.4090909090909091" RelY="1.2258064516129032"/> <Point X="340.0" Y="651.0" GraphId="e_265_1"/> <Point X="356.0" Y="700.0" GraphId="e_265_2" GraphRef="n126_REACTOME_216667" RelX="-0.17857142857142858" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.7149634998523121" GraphId="e_265_a_p"/> </Graphics> </Line> <Line GraphId="e_265_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="320.0" Y="651.0" GraphId="e_265_c__0_0" GraphRef="n119_REACTOME_437099" RelX="1.1666666666666667" RelY="0.0"/> <Point X="340.0" Y="651.0" GraphId="e_265_c__0_1" GraphRef="e_265_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_266_REACTOME_437084"> <Comment Source="WikiPathways-description">The human gene SLC30A3 encodes zinc transporter ZnT3. Through experiments on the mouse homologue Znt3, it is thought this transporter is expressed mainly in brain and testis and mediated the accumulation of zinc into synaptic vesicles (Palmiter et al, 1996).</Comment> <BiopaxRef>lit_437079</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="420.0" Y="500.0" GraphId="e_266_0" GraphRef="n125_REACTOME_29426" RelX="0.45454545454545453" RelY="-1.1612903225806452"/> <Point X="516.0" Y="360.0" GraphId="e_266_1"/> <Point X="565.0" Y="360.0" GraphId="e_266_2" GraphRef="n115_REACTOME_437093" RelX="-1.1363636363636365" RelY="-0.06451612903225806" ArrowHead="Arrow"/> <Anchor Position="0.7760028276290821" GraphId="e_266_a_p"/> </Graphics> </Line> <Line GraphId="e_266_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="514.0" Y="340.0" GraphId="e_266_c__0_0" GraphRef="n120_REACTOME_437087" RelX="0.0" RelY="1.3043478260869565"/> <Point X="516.0" Y="360.0" GraphId="e_266_c__0_1" GraphRef="e_266_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_267_REACTOME_437129"> <Comment Source="WikiPathways-description">The human gene SLC30A7 encodes the zinc transporter ZnT7. It is thought to be present in the small intestine and lung in humans (Kirschke CP and Huang L, 2003). Functional properties assigned to ZnT7 are based on studies conducted with mouse experiments.</Comment> <BiopaxRef>lit_437130</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="407.0" Y="537.0" GraphId="e_267_0" GraphRef="n125_REACTOME_29426" RelX="-0.13636363636363635" RelY="1.2258064516129032"/> <Point X="391.0" Y="652.0" GraphId="e_267_1"/> <Point X="368.0" Y="700.0" GraphId="e_267_2" GraphRef="n126_REACTOME_216667" RelX="0.25" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.6856741941256701" GraphId="e_267_a_p"/> </Graphics> </Line> <Line GraphId="e_267_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="410.0" Y="650.0" GraphId="e_267_c__0_0" GraphRef="n127_REACTOME_437104" RelX="-1.1666666666666667" RelY="0.0"/> <Point X="391.0" Y="652.0" GraphId="e_267_c__0_1" GraphRef="e_267_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_268_REACTOME_435375"> <Comment Source="WikiPathways-description">The human gene SLC30A2 encodes zinc transporter ZnT2. Its function is inferred from experiments using rat Znt2 (Palmiter RD et al, 1996).</Comment> <BiopaxRef>lit_435352</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="435.0" Y="516.0" GraphId="e_268_0" GraphRef="n125_REACTOME_29426" RelX="1.1363636363636365" RelY="-0.12903225806451613"/> <Point X="517.0" Y="509.0" GraphId="e_268_1"/> <Point X="575.0" Y="509.0" GraphId="e_268_2" GraphRef="n116_REACTOME_435350" RelX="-1.1363636363636365" RelY="-0.06451612903225806" ArrowHead="Arrow"/> <Anchor Position="0.5865949510748332" GraphId="e_268_a_p"/> </Graphics> </Line> <Line GraphId="e_268_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="517.0" Y="477.0" GraphId="e_268_c__0_0" GraphRef="n123_REACTOME_435363" RelX="0.0" RelY="1.3043478260869565"/> <Point X="517.0" Y="509.0" GraphId="e_268_c__0_1" GraphRef="e_268_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_269_REACTOME_435366"> <Comment Source="WikiPathways-description">The human gene SLC30A1 encodes the zinc transporter ZnT1. It is widely expressed throughout the body and it's expression is regulated by zinc. ZnT1 is the only member of the SLC30 gene family that is located on the plasma membrane and mediates the transport of zinc out of the cell (Devergnas S et al, 2004).</Comment> <BiopaxRef>lit_435379</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="385.0" Y="518.0" GraphId="e_269_0" GraphRef="n125_REACTOME_29426" RelX="-1.1363636363636365" RelY="0.0"/> <Point X="250.0" Y="520.0" GraphId="e_269_1"/> <Point X="176.0" Y="521.0" GraphId="e_269_2" GraphRef="n122_REACTOME_158417" RelX="1.1363636363636365" RelY="-0.06451612903225806" ArrowHead="Arrow"/> <Anchor Position="0.6459372289239466" GraphId="e_269_a_p"/> </Graphics> </Line> <Line GraphId="e_269_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="249.0" Y="499.0" GraphId="e_269_c__0_0" GraphRef="n121_REACTOME_435361" RelX="0.0" RelY="1.3043478260869565"/> <Point X="250.0" Y="520.0" GraphId="e_269_c__0_1" GraphRef="e_269_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_270_REACTOME_437136"> <Comment Source="WikiPathways-description">The human SLC30A8 gene encodes the zinc transporter ZnT8 which is specifically expressed in pancreatic beta cells. Zinc is required for zinc-insulin crystallization within secretory vesicles of these cells. After glucose stimulation, large amounts of zinc are secreted locally in the extracellular matrix together with insulin. It has been suggested that this co-secreted zinc plays a role in islet cell paracrine and/or autocrine communication&lt;br&gt;(Chimienti F et al, 2006).</Comment> <BiopaxRef>lit_264356</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="419.0" Y="537.0" GraphId="e_270_0" GraphRef="n125_REACTOME_29426" RelX="0.4090909090909091" RelY="1.2258064516129032"/> <Point X="522.0" Y="707.0" GraphId="e_270_1"/> <Point X="600.0" Y="706.0" GraphId="e_270_2" GraphRef="n118_REACTOME_216785" RelX="-1.1071428571428572" RelY="0.0" ArrowHead="Arrow"/> <Anchor Position="0.7181596017437942" GraphId="e_270_a_p"/> </Graphics> </Line> <Line GraphId="e_270_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="523.0" Y="729.0" GraphId="e_270_c__0_0" GraphRef="n124_REACTOME_437106" RelX="-0.05555555555555555" RelY="-1.2173913043478262"/> <Point X="522.0" Y="707.0" GraphId="e_270_c__0_1" GraphRef="e_270_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_271_REACTOME_437085"> <Comment Source="WikiPathways-description">The human gene SLC30A5 encodes the zinc transporter ZnT5. This protein is widely expressed but is most abundant in pancreatic beta cells (Kambe T et al, 2002). In these cells, ZnT5 mediates the transport of zinc into secretory granules that contain insulin.</Comment> <BiopaxRef>lit_437091</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="421.0" Y="537.0" GraphId="e_271_0" GraphRef="n125_REACTOME_29426" RelX="0.5" RelY="1.2258064516129032"/> <Point X="522.0" Y="673.0" GraphId="e_271_1"/> <Point X="600.0" Y="697.0" GraphId="e_271_2" GraphRef="n118_REACTOME_216785" RelX="-1.1071428571428572" RelY="-0.5806451612903226" ArrowHead="Arrow"/> <Anchor Position="0.6748791221616429" GraphId="e_271_a_p"/> </Graphics> </Line> <Line GraphId="e_271_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="523.0" Y="652.0" GraphId="e_271_c__0_0" GraphRef="n117_REACTOME_437105" RelX="-0.05555555555555555" RelY="1.3043478260869565"/> <Point X="522.0" Y="673.0" GraphId="e_271_c__0_1" GraphRef="e_271_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_272_REACTOME_442393"> <Comment Source="WikiPathways-description">The human gene SLC39A7 encodes the zinc transporter ZIP7 (HKE4, Histidine-rich membrane protein Ke4). It is expressed in many tissues but especially in liver, kidney and the hormonal tissues apart from brain. Unlike the other members of the LZT subfamily, ZIP7 is localized to intracellular membranes of the ER rather than the plasma membrane and mediates zinc efflux into the cytoplasm (Taylor KM et al, 2004).</Comment> <BiopaxRef>lit_442347</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="862.0" Y="583.0" GraphId="e_272_0" GraphRef="n133_REACTOME_442320" RelX="1.1363636363636365" RelY="0.0"/> <Point X="919.0" Y="583.0" GraphId="e_272_1"/> <Point X="1003.0" Y="625.0" GraphId="e_272_2" GraphRef="n135_REACTOME_29426" RelX="-1.1363636363636365" RelY="-0.7096774193548387" ArrowHead="Arrow"/> <Anchor Position="0.3776964168254347" GraphId="e_272_a_p"/> </Graphics> </Line> <Line GraphId="e_272_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="919.0" Y="555.0" GraphId="e_272_c__0_0" GraphRef="n129_REACTOME_442363" RelX="-0.06060606060606061" RelY="1.3043478260869565"/> <Point X="919.0" Y="583.0" GraphId="e_272_c__0_1" GraphRef="e_272_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_273_REACTOME_442317"> <Comment Source="WikiPathways-description">The human gene SLC39A6 encodes the zinc transporter ZIP6 (LIV-1). The gene is oestrogen-regulated and has been implicated in metastatic breast cancer. ZIP6 mediates the transport of zinc into cells, is localized to the plasma membrane and is expressed mainly in hormonal tissues such as breast, prostate and brain (Taylor KM et al, 2003).&lt;br&gt;&lt;br&gt;The human gene SLC39A14 encodes the zinc transporter ZIP14. This protein is ubiquitously expressed with higher expression seen in heart, liver and pancreas. ZIP14 is localized to the plasma membrane and mediates zinc influx into cells (Taylor KM et al, 2005).</Comment> <BiopaxRef>lit_442413</BiopaxRef> <BiopaxRef>lit_442371</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1014.0" Y="1018.0" GraphId="e_273_0" GraphRef="n136_REACTOME_158417" RelX="-0.6363636363636364" RelY="-1.1612903225806452"/> <Point X="841.0" Y="827.0" GraphId="e_273_1"/> <Point X="1012.0" Y="655.0" GraphId="e_273_2" GraphRef="n135_REACTOME_29426" RelX="-0.7272727272727273" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.5151554452016897" GraphId="e_273_a_p"/> </Graphics> </Line> <Line GraphId="e_273_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="822.0" Y="826.0" GraphId="e_273_c__0_0" GraphRef="n132_REACTOME_442330" RelX="1.088235294117647" RelY="0.08695652173913043"/> <Point X="841.0" Y="827.0" GraphId="e_273_c__0_1" GraphRef="e_273_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_274_REACTOME_442387"> <Comment Source="WikiPathways-description">The human gene SLC39A8 encodes the zinc transporter ZIP8 (BIGM103, BCG-induced integral membrane protein in monocyte clone 103 protein). It is highly expressed in the pancreas and localized to the plasma membrane where it mediates the influx of zinc into the cell (Besecker B et al, 2008). The highly homologous mouse ZIP8 have been shown to play important roles in regulating zinc homeostasis and determining sensitivity to cadmium toxicity in mouse testicular endothelium and kidney tissue. It is expected the human transporter plays a similar role (He L et al, 2009). ZIP8 belongs to the LZT subfamily of ZIP transporters.</Comment> <BiopaxRef>lit_445734</BiopaxRef> <BiopaxRef>lit_446537</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1028.0" Y="1018.0" GraphId="e_274_0" GraphRef="n136_REACTOME_158417" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="1028.0" Y="828.0" GraphId="e_274_1"/> <Point X="1028.0" Y="655.0" GraphId="e_274_2" GraphRef="n135_REACTOME_29426" RelX="0.0" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.5234159779614325" GraphId="e_274_a_p"/> </Graphics> </Line> <Line GraphId="e_274_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1011.0" Y="827.0" GraphId="e_274_c__0_0" GraphRef="n134_REACTOME_442328" RelX="1.2121212121212122" RelY="0.0"/> <Point X="1028.0" Y="828.0" GraphId="e_274_c__0_1" GraphRef="e_274_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_275_REACTOME_442422"> <Comment Source="WikiPathways-description">The human gene SLC39A1 encodes the zinc transporter hZIP1. It is ubiquitously expressed (Lioumi M et al, 1999) and mediates the influx of zinc into cells (Gaither LA and Eide DJ, 2001).&lt;br&gt;The human gene SLC39A2 encodes the zinc transporter hZIP2. It is expressed exclusively in prostate and uterine epithelial cells and mediates zinc transport into cells (Gaither LA and Eide DJ, 2000).&lt;br&gt;&lt;br&gt;Normal prostate cells have the ability to accumulate high levels of zinc. In prostate cancer, hZIP1-3 transporters are down-regulated and the cells lose the ability to accumulate zinc. Zinc plays a role as a tumour-suppressing agent thus prostate cells can become cancerous. Silencing of the genes that express hZIP1-3 transporters is a required event for malignancy (Costello LC et al, 1999; Desouki MM et al, 2007).&lt;br&gt;&lt;br&gt;The human gene SLC39A4 encodes the zinc transporter hZIP4 (Kury S et al, 2002). The role of zinc in tumour progression is complicated and, subsequently, so are the role of ZIP transporters. For example, ZIP4 can actually enhance cancer progression (Li M et al, 2007; Li M et al, 2009). Defects in SLC39A4 result in the inherited condition acrodermatitis enteropathica (AE) results from defective absorption of dietary zinc from the duodenum and jejunum. Clinical features include growth retardation, immune system dysfunction, severe dermatitis and mental disorders (Wang K et al, 2002).</Comment> <BiopaxRef>lit_442365</BiopaxRef> <BiopaxRef>lit_442343</BiopaxRef> <BiopaxRef>lit_442382</BiopaxRef> <BiopaxRef>lit_442348</BiopaxRef> <BiopaxRef>lit_442418</BiopaxRef> <BiopaxRef>lit_442409</BiopaxRef> <BiopaxRef>lit_442385</BiopaxRef> <BiopaxRef>lit_445725</BiopaxRef> <BiopaxRef>lit_445722</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1021.0" Y="1018.0" GraphId="e_275_0" GraphRef="n136_REACTOME_158417" RelX="-0.3181818181818182" RelY="-1.1612903225806452"/> <Point X="938.0" Y="825.0" GraphId="e_275_1"/> <Point X="1020.0" Y="655.0" GraphId="e_275_2" GraphRef="n135_REACTOME_29426" RelX="-0.36363636363636365" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.5267620898079899" GraphId="e_275_a_p"/> </Graphics> </Line> <Line GraphId="e_275_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="919.0" Y="825.0" GraphId="e_275_c__0_0" GraphRef="n128_REACTOME_442327" RelX="1.1372549019607843" RelY="0.0"/> <Point X="938.0" Y="825.0" GraphId="e_275_c__0_1" GraphRef="e_275_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_276_REACTOME_442345"> <Comment Source="WikiPathways-description">The human gene SLC39A10 encodes the zinc transporter hZIP10. It is thought to be involved in the invasive behaviour of breast cancer cells where depletion of hZIP10 and intracellular zinc levels inhibit the migratory effects these cells (Kagara N et al, 2007). Functional characterization of this transporter was elucidated in the rat orthologue rZip10.</Comment> <BiopaxRef>lit_442391</BiopaxRef> <BiopaxRef>lit_442341</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1034.0" Y="1018.0" GraphId="e_276_0" GraphRef="n136_REACTOME_158417" RelX="0.2727272727272727" RelY="-1.1612903225806452"/> <Point X="1118.0" Y="828.0" GraphId="e_276_1"/> <Point X="1035.0" Y="655.0" GraphId="e_276_2" GraphRef="n135_REACTOME_29426" RelX="0.3181818181818182" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.519843896504967" GraphId="e_276_a_p"/> </Graphics> </Line> <Line GraphId="e_276_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1101.0" Y="828.0" GraphId="e_276_c__0_0" GraphRef="n130_REACTOME_442377" RelX="1.148936170212766" RelY="-0.08695652173913043"/> <Point X="1118.0" Y="828.0" GraphId="e_276_c__0_1" GraphRef="e_276_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_277_REACTOME_442405"> <Comment Source="WikiPathways-description">The human gene SLC39A5 encodes the zinc transporter hZIP5 (Wang F et al, 2004). Highest expressions are seen in liver, kidney, pancreas and throughout the small intestine and colon with little expression detected in other tissues. hZIP5 is localized to the basolateral membrane of cells in these tissues. The functionality of ZIP5 as a zinc transporter was determined using mouse protein (mZIP5) (Wang F et al, 2004).</Comment> <BiopaxRef>lit_442342</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1040.0" Y="1018.0" GraphId="e_277_0" GraphRef="n136_REACTOME_158417" RelX="0.5454545454545454" RelY="-1.1612903225806452"/> <Point X="1197.0" Y="826.0" GraphId="e_277_1"/> <Point X="1041.0" Y="655.0" GraphId="e_277_2" GraphRef="n135_REACTOME_29426" RelX="0.5909090909090909" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.5172592230591266" GraphId="e_277_a_p"/> </Graphics> </Line> <Line GraphId="e_277_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1182.0" Y="826.0" GraphId="e_277_c__0_0" GraphRef="n131_REACTOME_442360" RelX="1.15" RelY="-0.08695652173913043"/> <Point X="1197.0" Y="826.0" GraphId="e_277_c__0_1" GraphRef="e_277_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_278_REACTOME_444416"> <Comment Source="WikiPathways-description">The human gene RhAG encodes a Rhesus blood group family type A glycoprotein which is expressed specifically in erythroid cells. It is thought to mediate ammonium export from these cells (Marini AM et al, 2000; Westhoff CM et al, 2002). Defects in RHAG are the cause of regulator type Rh-null hemolytic anemia (RHN) (Rh-deficiency syndrome). RHN is a form of chronic hemolytic anemia (Hyland CA et al, 1998).</Comment> <BiopaxRef>lit_444394</BiopaxRef> <BiopaxRef>lit_444404</BiopaxRef> <BiopaxRef>lit_444409</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4090.0" Y="193.0" GraphId="e_278_0" GraphRef="n229_REACTOME_31633" RelX="-0.041666666666666664" RelY="-1.1612903225806452"/> <Point X="4090.0" Y="158.0" GraphId="e_278_1"/> <Point X="4090.0" Y="117.0" GraphId="e_278_2" GraphRef="n230_REACTOME_140912" RelX="0.0" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.4605263157894737" GraphId="e_278_a_p"/> </Graphics> </Line> <Line GraphId="e_278_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4111.0" Y="157.0" GraphId="e_278_c__0_0" GraphRef="n141_REACTOME_444408" RelX="-1.1428571428571428" RelY="0.0"/> <Point X="4090.0" Y="158.0" GraphId="e_278_c__0_1" GraphRef="e_278_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_279_REACTOME_444419"> <Comment Source="WikiPathways-description">The human gene RhBG encodes a Rhesus blood group family type B glycoprotein which is expressed mainly in the kidney but is also found in the liver. The liver and kidney are important tissues for ammonium metabolism and excretion. RhBG is located on the basolateral membrane and mediates the reversible transport of ammonium in and out of renal collecting duct cells in an electroneutral manner, with H+ transported the other way (Ludewig U, 2004; Liu Z et al, 2001).</Comment> <BiopaxRef>lit_444417</BiopaxRef> <BiopaxRef>lit_444423</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3786.0" Y="218.0" GraphId="e_279_0"/> <Point X="3787.0" Y="158.0" GraphId="e_279_1"/> <Point X="3786.0" Y="86.0" GraphId="e_279_2"/> <Anchor Position="0.0" GraphId="e_279_a_i"/> <Anchor Position="0.4545559739756358" GraphId="e_279_a_p"/> <Anchor Position="1.0" GraphId="e_279_a_o"/> </Graphics> </Line> <Line GraphId="e_279_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3786.0" Y="68.0" GraphId="e_279_i0_0" GraphRef="n142_REACTOME_351626" RelX="0.0" RelY="1.2258064516129032"/> <Point X="3786.0" Y="218.0" GraphId="e_279_i0_1" GraphRef="e_279_a_i"/> </Graphics> </Line> <Line GraphId="e_279_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3820.0" Y="269.0" GraphId="e_279_i1_0" GraphRef="n232_REACTOME_31633" RelX="-0.4166666666666667" RelY="-1.1612903225806452"/> <Point X="3786.0" Y="218.0" GraphId="e_279_i1_1" GraphRef="e_279_a_i"/> </Graphics> </Line> <Line GraphId="e_279_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3786.0" Y="250.0" GraphId="e_279_o0_0" ArrowHead="Arrow" GraphRef="n144_REACTOME_70106" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="3786.0" Y="86.0" GraphId="e_279_o0_1" GraphRef="e_279_a_o"/> </Graphics> </Line> <Line GraphId="e_279_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3814.0" Y="43.0" GraphId="e_279_o1_0" ArrowHead="Arrow" GraphRef="n231_REACTOME_140912" RelX="-0.4166666666666667" RelY="1.2258064516129032"/> <Point X="3786.0" Y="86.0" GraphId="e_279_o1_1" GraphRef="e_279_a_o"/> </Graphics> </Line> <Line GraphId="e_279_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3802.0" Y="158.0" GraphId="e_279_c__0_0" GraphRef="n139_REACTOME_444422" RelX="-1.1162790697674418" RelY="0.0"/> <Point X="3787.0" Y="158.0" GraphId="e_279_c__0_1" GraphRef="e_279_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_280_REACTOME_444393"> <Comment Source="WikiPathways-description">The human gene RhCG encodes the Rhesus blood group family type C glycoprotein which is mainly expressed in kidney collecting duct but also found in testis. RhCG is located on the apical membrane and mediates the bi-directional transport of ammonium into and out of renal collecting duct cells in an electroneutral manner, with H+ transported the other way (Liu Z et al, 2000; Marini AM et al, 2000).</Comment> <BiopaxRef>lit_444415</BiopaxRef> <BiopaxRef>lit_444394</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4039.0" Y="83.0" GraphId="e_280_0"/> <Point X="4040.0" Y="160.0" GraphId="e_280_1"/> <Point X="4040.0" Y="222.0" GraphId="e_280_2"/> <Anchor Position="0.0" GraphId="e_280_a_i"/> <Anchor Position="0.5539776699768663" GraphId="e_280_a_p"/> <Anchor Position="1.0" GraphId="e_280_a_o"/> </Graphics> </Line> <Line GraphId="e_280_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4008.0" Y="44.0" GraphId="e_280_i0_0" GraphRef="n137_REACTOME_140912" RelX="0.4583333333333333" RelY="1.2258064516129032"/> <Point X="4039.0" Y="83.0" GraphId="e_280_i0_1" GraphRef="e_280_a_i"/> </Graphics> </Line> <Line GraphId="e_280_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4040.0" Y="254.0" GraphId="e_280_i1_0" GraphRef="n145_REACTOME_70106" RelX="-0.0625" RelY="-1.1612903225806452"/> <Point X="4039.0" Y="83.0" GraphId="e_280_i1_1" GraphRef="e_280_a_i"/> </Graphics> </Line> <Line GraphId="e_280_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4011.0" Y="274.0" GraphId="e_280_o0_0" ArrowHead="Arrow" GraphRef="n140_REACTOME_31633" RelX="0.3333333333333333" RelY="-1.1612903225806452"/> <Point X="4040.0" Y="222.0" GraphId="e_280_o0_1" GraphRef="e_280_a_o"/> </Graphics> </Line> <Line GraphId="e_280_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4039.0" Y="65.0" GraphId="e_280_o1_0" ArrowHead="Arrow" GraphRef="n143_REACTOME_351626" RelX="0.0" RelY="1.2258064516129032"/> <Point X="4040.0" Y="222.0" GraphId="e_280_o1_1" GraphRef="e_280_a_o"/> </Graphics> </Line> <Line GraphId="e_280_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4023.0" Y="160.0" GraphId="e_280_c__0_0" GraphRef="n138_REACTOME_444397" RelX="1.1363636363636365" RelY="0.0"/> <Point X="4040.0" Y="160.0" GraphId="e_280_c__0_1" GraphRef="e_280_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_281_REACTOME_351963"> <Comment Source="WikiPathways-description">The protein SLC6A18 was first identified as an amino acid transporter based on sequence similarity to other members of the SLC6 protein family (Hoglund et al. 2005). It is annotated here as mediating glycine uptake based on the phenotype of mice homozygous for a null mutation in the homologous gene (Quan et al. 2004).</Comment> <BiopaxRef>lit_351988</BiopaxRef> <BiopaxRef>lit_351981</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3789.0" Y="940.0" GraphId="e_281_0" GraphRef="n181_REACTOME_266029" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="3789.0" Y="828.0" GraphId="e_281_1"/> <Point X="3789.0" Y="729.0" GraphId="e_281_2" GraphRef="n180_REACTOME_29424" RelX="-0.037037037037037035" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.5308056872037915" GraphId="e_281_a_p"/> </Graphics> </Line> <Line GraphId="e_281_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3765.0" Y="828.0" GraphId="e_281_c__0_0" GraphRef="n179_REACTOME_352020" RelX="1.1" RelY="0.0"/> <Point X="3789.0" Y="828.0" GraphId="e_281_c__0_1" GraphRef="e_281_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_282_REACTOME_379393"> <Comment Source="WikiPathways-description">The human gene SLC6A3 encodes the sodium-dependent dopamine transporter, DAT which mediates the re-uptake of dopamine from the synaptic cleft (Vandenbergh DJ et al, 2000). Dopamine can then be degraded by either COMT or monoamine oxidase.</Comment> <BiopaxRef>lit_379480</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3259.0" Y="883.0" GraphId="e_282_0"/> <Point X="3259.0" Y="825.0" GraphId="e_282_1"/> <Point X="3259.0" Y="784.0" GraphId="e_282_2"/> <Anchor Position="0.0" GraphId="e_282_a_i"/> <Anchor Position="0.5858585858585859" GraphId="e_282_a_p"/> <Anchor Position="1.0" GraphId="e_282_a_o"/> </Graphics> </Line> <Line GraphId="e_282_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3259.0" Y="951.0" GraphId="e_282_i0_0" GraphRef="n183_REACTOME_380873" RelX="-0.02702702702702703" RelY="-1.1612903225806452"/> <Point X="3259.0" Y="883.0" GraphId="e_282_i0_1" GraphRef="e_282_a_i"/> </Graphics> </Line> <Line GraphId="e_282_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3236.0" Y="894.0" GraphId="e_282_i1_0" GraphRef="n219_REACTOME_74113" RelX="0.6666666666666666" RelY="-1.1612903225806452"/> <Point X="3259.0" Y="883.0" GraphId="e_282_i1_1" GraphRef="e_282_a_i"/> </Graphics> </Line> <Line GraphId="e_282_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3259.0" Y="726.0" GraphId="e_282_o0_0" ArrowHead="Arrow" GraphRef="n170_REACTOME_159362" RelX="0.0" RelY="1.2258064516129032"/> <Point X="3259.0" Y="784.0" GraphId="e_282_o0_1" GraphRef="e_282_a_o"/> </Graphics> </Line> <Line GraphId="e_282_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3224.0" Y="764.0" GraphId="e_282_o1_0" ArrowHead="Arrow" GraphRef="n207_REACTOME_83910" RelX="0.5897435897435898" RelY="1.2258064516129032"/> <Point X="3259.0" Y="784.0" GraphId="e_282_o1_1" GraphRef="e_282_a_o"/> </Graphics> </Line> <Line GraphId="e_282_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3238.0" Y="825.0" GraphId="e_282_c__0_0" GraphRef="n171_REACTOME_379482" RelX="1.054263565891473" RelY="-0.05263157894736842"/> <Point X="3259.0" Y="825.0" GraphId="e_282_c__0_1" GraphRef="e_282_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_283_REACTOME_352029"> <Comment Source="WikiPathways-description">The plasma membrane transport protein SLC6A12 (BGT-1) mediates the uptake of GABA (gamma-aminobutyrate) and betaine and, less efficiently, of diminobutyrate (DABA) and beta-alanine. Together with each amino acid molecule, 3 sodium ions and 2 chloride ions are taken up. In the body, SLC6A12 is expressed in the proximal tubules of the kidney and cells of the central nervous system (Rasola et al. 1995; Matskevitch et al. 1999).</Comment> <BiopaxRef>lit_352038</BiopaxRef> <BiopaxRef>lit_351985</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4709.0" Y="421.0" GraphId="e_283_0"/> <Point X="4660.0" Y="421.0" GraphId="e_283_1"/> <Point X="4594.0" Y="420.0" GraphId="e_283_2"/> <Anchor Position="0.0" GraphId="e_283_a_i"/> <Anchor Position="0.4260588910117653" GraphId="e_283_a_p"/> <Anchor Position="1.0" GraphId="e_283_a_o"/> </Graphics> </Line> <Line GraphId="e_283_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4788.0" Y="422.0" GraphId="e_283_i0_0" GraphRef="n147_REACTOME_352007" RelX="-1.046875" RelY="-0.08695652173913043"/> <Point X="4709.0" Y="421.0" GraphId="e_283_i0_1" GraphRef="e_283_a_i"/> </Graphics> </Line> <Line GraphId="e_283_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4770.0" Y="452.0" GraphId="e_283_i1_0" GraphRef="n192_REACTOME_188972" RelX="-0.9206349206349206" RelY="-1.1612903225806452"/> <Point X="4709.0" Y="421.0" GraphId="e_283_i1_1" GraphRef="e_283_a_i"/> </Graphics> </Line> <Line GraphId="e_283_i2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4769.0" Y="393.0" GraphId="e_283_i2_0" GraphRef="n217_REACTOME_74113" RelX="-0.7692307692307693" RelY="1.2258064516129032"/> <Point X="4709.0" Y="421.0" GraphId="e_283_i2_1" GraphRef="e_283_a_i"/> </Graphics> </Line> <Line GraphId="e_283_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4509.0" Y="421.0" GraphId="e_283_o0_0" ArrowHead="Arrow" GraphRef="n146_REACTOME_351982" RelX="1.046875" RelY="-0.043478260869565216"/> <Point X="4594.0" Y="420.0" GraphId="e_283_o0_1" GraphRef="e_283_a_o"/> </Graphics> </Line> <Line GraphId="e_283_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4541.0" Y="444.0" GraphId="e_283_o1_0" ArrowHead="Arrow" GraphRef="n185_REACTOME_352022" RelX="1.1111111111111112" RelY="-0.9032258064516129"/> <Point X="4594.0" Y="420.0" GraphId="e_283_o1_1" GraphRef="e_283_a_o"/> </Graphics> </Line> <Line GraphId="e_283_o2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4538.0" Y="398.0" GraphId="e_283_o2_0" ArrowHead="Arrow" GraphRef="n204_REACTOME_83910" RelX="1.0769230769230769" RelY="0.8387096774193549"/> <Point X="4594.0" Y="420.0" GraphId="e_283_o2_1" GraphRef="e_283_a_o"/> </Graphics> </Line> <Line GraphId="e_283_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4660.0" Y="384.0" GraphId="e_283_c__0_0" GraphRef="n165_REACTOME_351969" RelX="-0.03333333333333333" RelY="1.3043478260869565"/> <Point X="4660.0" Y="421.0" GraphId="e_283_c__0_1" GraphRef="e_283_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_284_REACTOME_351987"> <Comment Source="WikiPathways-description">The plasma membrane transport protein SLC6A6 mediates the uptake of taurine and beta-alanine. Together with each amino acid molecule, 2 sodium ions and 1 chloride ion are taken up. 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They terminates the action of GABA by high affinity sodium-dependent reuptake into presynaptic terminals. Transport of GABA by GAT1-3 is proposed to be accompanied by 2Na+ ions and 1 Cl- ion (Loo DD et al, 2000).&lt;br&gt;&lt;br&gt;SLC6A1 encodes a sodium- and chloride-dependent GABA transporter 1, GAT1, which is the predominant GABA transporter in brain. It is widely distributed in the brain and co-localized to GABAergic neurons (Nelson H et al, 1990). SLC6A13 encodes a sodium- and chloride-dependent GABA transporter 2, GAT2, which is localized to GABAergic neurons in the brain. It is also found in retina, liver and kidney (Christiansen B et al, 2007). SLC6A11 encodes a sodium- and chloride-dependent GABA transporter 3, GAT3. It is expressed in the brain and localizes to GABAergic neurons (Borden LA et al, 1994).</Comment> <BiopaxRef>lit_444034</BiopaxRef> <BiopaxRef>lit_444023</BiopaxRef> <BiopaxRef>lit_444013</BiopaxRef> <BiopaxRef>lit_444016</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3026.0" Y="952.0" GraphId="e_286_0"/> <Point X="3026.0" Y="828.0" GraphId="e_286_1"/> <Point X="3026.0" Y="748.0" GraphId="e_286_2"/> <Anchor Position="0.0" GraphId="e_286_a_i"/> <Anchor Position="0.6078431372549019" GraphId="e_286_a_p"/> <Anchor Position="1.0" GraphId="e_286_a_o"/> </Graphics> </Line> <Line GraphId="e_286_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3027.0" Y="1014.0" GraphId="e_286_i0_0" GraphRef="n166_REACTOME_352003" RelX="-0.0425531914893617" RelY="-1.1612903225806452"/> <Point X="3026.0" Y="952.0" GraphId="e_286_i0_1" GraphRef="e_286_a_i"/> </Graphics> </Line> <Line GraphId="e_286_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2995.0" Y="966.0" GraphId="e_286_i1_0" GraphRef="n196_REACTOME_188972" RelX="0.8888888888888888" RelY="-1.1612903225806452"/> <Point X="3026.0" Y="952.0" GraphId="e_286_i1_1" GraphRef="e_286_a_i"/> </Graphics> </Line> <Line GraphId="e_286_i2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3064.0" Y="973.0" GraphId="e_286_i2_0" GraphRef="n216_REACTOME_74113" RelX="-0.6666666666666666" RelY="-1.1612903225806452"/> <Point X="3026.0" Y="952.0" GraphId="e_286_i2_1" GraphRef="e_286_a_i"/> </Graphics> </Line> <Line GraphId="e_286_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3027.0" Y="675.0" GraphId="e_286_o0_0" ArrowHead="Arrow" GraphRef="n175_REACTOME_352011" RelX="-0.0425531914893617" RelY="1.2258064516129032"/> <Point X="3026.0" Y="748.0" GraphId="e_286_o0_1" GraphRef="e_286_a_o"/> </Graphics> </Line> <Line GraphId="e_286_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2986.0" Y="726.0" GraphId="e_286_o1_0" ArrowHead="Arrow" GraphRef="n189_REACTOME_352022" RelX="0.7619047619047619" RelY="1.2258064516129032"/> <Point X="3026.0" Y="748.0" GraphId="e_286_o1_1" GraphRef="e_286_a_o"/> </Graphics> </Line> <Line GraphId="e_286_o2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3069.0" Y="722.0" GraphId="e_286_o2_0" ArrowHead="Arrow" GraphRef="n206_REACTOME_83910" RelX="-0.6153846153846154" RelY="1.2258064516129032"/> <Point X="3026.0" Y="748.0" GraphId="e_286_o2_1" GraphRef="e_286_a_o"/> </Graphics> </Line> <Line GraphId="e_286_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3002.0" Y="827.0" GraphId="e_286_c__0_0" GraphRef="n182_REACTOME_444011" RelX="1.0843373493975903" RelY="0.0"/> <Point X="3026.0" Y="828.0" GraphId="e_286_c__0_1" GraphRef="e_286_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_287_REACTOME_380620"> <Comment Source="WikiPathways-description">The human gene SLC6A4 encodes the sodium-dependent serotonin transporter 5HTT which mediates the re-uptake of serotonin from the synaptic cleft thus terminating the action of serotonin (Canli T and Lesch KP, 2007). 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Its action is terminated by rapid re-uptake into the pre-synaptic terminal or surrounding glial cells. This re-uptake is mediated by the sodium- and chloride-dependent glycine transporters 1 and 2 (GLYT1 and GLYT2 respectively). GLYT1 is encoded by the human gene SLC5A9 and is expressed in the brain, liver, kidney, pancreas, lung and placenta (Kim KM et al, 1994). GLYT2 is encoded by the human gene SLC6A5 and is predominantly expressed in the medulla (Morrow JA et al, 1998). Defects in SLC6A5 cause startle disease (STHE or hyperekplexia). STHE is is a human neurological disorder characterized by an excessive startle response (Rees MI et al, 2006).</Comment> <BiopaxRef>lit_444138</BiopaxRef> <BiopaxRef>lit_444097</BiopaxRef> <BiopaxRef>lit_444103</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3934.0" Y="956.0" GraphId="e_288_0"/> <Point X="3934.0" Y="827.0" GraphId="e_288_1"/> <Point X="3934.0" Y="711.0" GraphId="e_288_2"/> <Anchor Position="0.0" GraphId="e_288_a_i"/> <Anchor Position="0.5265306122448979" GraphId="e_288_a_p"/> <Anchor Position="1.0" GraphId="e_288_a_o"/> </Graphics> </Line> <Line GraphId="e_288_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3820.0" Y="957.0" GraphId="e_288_i0_0" GraphRef="n181_REACTOME_266029" RelX="1.1071428571428572" RelY="-0.06451612903225806"/> <Point X="3934.0" Y="956.0" GraphId="e_288_i0_1" GraphRef="e_288_a_i"/> </Graphics> </Line> <Line GraphId="e_288_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3902.0" Y="1001.0" GraphId="e_288_i1_0" GraphRef="n193_REACTOME_188972" RelX="0.31746031746031744" RelY="-1.1612903225806452"/> <Point X="3934.0" Y="956.0" GraphId="e_288_i1_1" GraphRef="e_288_a_i"/> </Graphics> </Line> <Line GraphId="e_288_i2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3965.0" Y="1003.0" GraphId="e_288_i2_0" GraphRef="n214_REACTOME_74113" RelX="-0.2564102564102564" RelY="-1.1612903225806452"/> <Point X="3934.0" Y="956.0" GraphId="e_288_i2_1" GraphRef="e_288_a_i"/> </Graphics> </Line> <Line GraphId="e_288_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3820.0" Y="710.0" GraphId="e_288_o0_0" ArrowHead="Arrow" GraphRef="n180_REACTOME_29424" RelX="1.1111111111111112" RelY="0.0"/> <Point X="3934.0" Y="711.0" GraphId="e_288_o0_1" GraphRef="e_288_a_o"/> </Graphics> </Line> <Line GraphId="e_288_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3900.0" Y="671.0" GraphId="e_288_o1_0" ArrowHead="Arrow" GraphRef="n188_REACTOME_352022" RelX="0.3492063492063492" RelY="1.2258064516129032"/> <Point X="3934.0" Y="711.0" GraphId="e_288_o1_1" GraphRef="e_288_a_o"/> </Graphics> </Line> <Line GraphId="e_288_o2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3963.0" Y="676.0" GraphId="e_288_o2_0" ArrowHead="Arrow" GraphRef="n200_REACTOME_83910" RelX="-0.3076923076923077" RelY="1.2258064516129032"/> <Point X="3934.0" Y="711.0" GraphId="e_288_o2_1" GraphRef="e_288_a_o"/> </Graphics> </Line> <Line GraphId="e_288_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3903.0" Y="826.0" GraphId="e_288_c__0_0" GraphRef="n176_REACTOME_444088" RelX="1.1578947368421053" RelY="0.0"/> <Point X="3934.0" Y="827.0" GraphId="e_288_c__0_1" GraphRef="e_288_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_289_REACTOME_444160"> <Comment Source="WikiPathways-description">The human gene SLC18A1 encodes the vesicular monoamine transporter 1 (VMAT1) (Erickson JD et al, 1996). VMAT1 is mainly expressed in neuroendocrine cells. The human gene SLC18A2 encodes VMAT2 (Erickson JD and Eiden LE, 1993). Both transporters can mediate the transport of biogenic amines into secretory vesicles, which can then discharge their contents into the extracellular space by exocytosis. Predominant biogenic amines these proteins can transport are serotonin, dopamine, adrenaline, noradrenaline and histamine.</Comment> <BiopaxRef>lit_444155</BiopaxRef> <BiopaxRef>lit_444158</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="1114.0" Y="479.0" GraphId="e_289_0" GraphRef="n159_REACTOME_444154" RelX="1.0535714285714286" RelY="0.0"/> <Point X="1188.0" Y="481.0" GraphId="e_289_1"/> <Point X="1271.0" Y="481.0" GraphId="e_289_2" GraphRef="n148_REACTOME_444152" RelX="-1.0535714285714286" RelY="0.0" ArrowHead="Arrow"/> <Anchor Position="0.4714285548210221" GraphId="e_289_a_p"/> </Graphics> </Line> <Line GraphId="e_289_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="1188.0" Y="431.0" GraphId="e_289_c__0_0" GraphRef="n173_REACTOME_444147" RelX="-0.03636363636363636" RelY="1.3043478260869565"/> <Point X="1188.0" Y="481.0" GraphId="e_289_c__0_1" GraphRef="e_289_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_290_REACTOME_352052"> <Comment Source="WikiPathways-description">SLC6A20, associated with the plasma membrane, mediates the uptake of proline plus a sodium ion. 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NAT1 is a monoamine transporter that transports noradrenaline from the synapse back to its vesicles for storage until later use. NAT1 is encoded by the human gene SLC6A2 and is expressed in the CNS and adrenal gland (Pacholczyk T et al, 1991). 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Its actions are terminated by its re-uptake from the synaptic cleft into the pre-synaptic terminal in the brain. 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Uptake of one amino acid molecule is accompanied by uptake of two sodium ions and a chloride ion. As assessed by Northern blotting, SLC6A14 is expressed at high levels in lung but only at low levels, if at all, in intestine or kidney (Sloan and Mager 1999; Anderson et al. 2008).</Comment> <BiopaxRef>lit_375491</BiopaxRef> <BiopaxRef>lit_375465</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4504.0" Y="101.0" GraphId="e_295_0"/> <Point X="4504.0" Y="159.0" GraphId="e_295_1"/> <Point X="4504.0" Y="212.0" GraphId="e_295_2"/> <Anchor Position="0.0" GraphId="e_295_a_i"/> <Anchor Position="0.5225225225225225" GraphId="e_295_a_p"/> <Anchor Position="1.0" GraphId="e_295_a_o"/> </Graphics> </Line> <Line GraphId="e_295_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4503.0" Y="39.0" GraphId="e_295_i0_0" GraphRef="n158_REACTOME_375468" RelX="0.0" RelY="1.2258064516129032"/> <Point X="4504.0" Y="101.0" GraphId="e_295_i0_1" GraphRef="e_295_a_i"/> </Graphics> </Line> <Line GraphId="e_295_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4527.0" Y="90.0" GraphId="e_295_i1_0" GraphRef="n194_REACTOME_188972" RelX="-0.7936507936507936" RelY="1.2258064516129032"/> <Point X="4504.0" Y="101.0" GraphId="e_295_i1_1" GraphRef="e_295_a_i"/> </Graphics> </Line> <Line GraphId="e_295_i2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4477.0" Y="90.0" GraphId="e_295_i2_0" GraphRef="n209_REACTOME_74113" RelX="0.6923076923076923" RelY="1.2258064516129032"/> <Point X="4504.0" Y="101.0" GraphId="e_295_i2_1" GraphRef="e_295_a_i"/> </Graphics> </Line> <Line GraphId="e_295_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4504.0" Y="268.0" GraphId="e_295_o0_0" ArrowHead="Arrow" GraphRef="n163_REACTOME_375459" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="4504.0" Y="212.0" GraphId="e_295_o0_1" GraphRef="e_295_a_o"/> </Graphics> </Line> <Line GraphId="e_295_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4491.0" Y="218.0" GraphId="e_295_o1_0" ArrowHead="Arrow" GraphRef="n186_REACTOME_352022" RelX="1.1111111111111112" RelY="-0.9032258064516129"/> <Point X="4504.0" Y="212.0" GraphId="e_295_o1_1" GraphRef="e_295_a_o"/> </Graphics> </Line> <Line GraphId="e_295_o2"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4533.0" Y="224.0" GraphId="e_295_o2_0" ArrowHead="Arrow" GraphRef="n201_REACTOME_83910" RelX="-0.8205128205128205" RelY="-1.1612903225806452"/> <Point X="4504.0" Y="212.0" GraphId="e_295_o2_1" GraphRef="e_295_a_o"/> </Graphics> </Line> <Line GraphId="e_295_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4480.0" Y="159.0" GraphId="e_295_c__0_0" GraphRef="n162_REACTOME_375471" RelX="1.1" RelY="-0.17391304347826086"/> <Point X="4504.0" Y="159.0" GraphId="e_295_c__0_1" GraphRef="e_295_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_296_REACTOME_446278"> <Comment Source="WikiPathways-description">The human gene RhBG encodes a Rhesus blood group family type B glycoprotein which is expressed mainly in the kidney but is also found in the liver. The liver and kidney are important tissues for ammonium metabolism and excretion. RhBG is located on the basolateral membrane and mediates the reversible transport of ammonium in and out of renal collecting duct cells in an electroneutral manner, with H+ transported the other way (Ludewig U, 2004; Liu Z et al, 2001).</Comment> <BiopaxRef>lit_444423</BiopaxRef> <BiopaxRef>lit_444417</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3870.0" Y="92.0" GraphId="e_296_0"/> <Point X="3870.0" Y="160.0" GraphId="e_296_1"/> <Point X="3870.0" Y="216.0" GraphId="e_296_2"/> <Anchor Position="0.0" GraphId="e_296_a_i"/> <Anchor Position="0.5483870967741935" GraphId="e_296_a_p"/> <Anchor Position="1.0" GraphId="e_296_a_o"/> </Graphics> </Line> <Line GraphId="e_296_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3870.0" Y="247.0" GraphId="e_296_i0_0" GraphRef="n234_REACTOME_70106" RelX="-0.0625" RelY="-1.1612903225806452"/> <Point X="3870.0" Y="92.0" GraphId="e_296_i0_1" GraphRef="e_296_a_i"/> </Graphics> </Line> <Line GraphId="e_296_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3834.0" Y="43.0" GraphId="e_296_i1_0" GraphRef="n231_REACTOME_140912" RelX="0.4166666666666667" RelY="1.2258064516129032"/> <Point X="3870.0" Y="92.0" GraphId="e_296_i1_1" GraphRef="e_296_a_i"/> </Graphics> </Line> <Line GraphId="e_296_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3870.0" Y="70.0" GraphId="e_296_o0_0" ArrowHead="Arrow" GraphRef="n233_REACTOME_351626" RelX="-0.0625" RelY="1.2258064516129032"/> <Point X="3870.0" Y="216.0" GraphId="e_296_o0_1" GraphRef="e_296_a_o"/> </Graphics> </Line> <Line GraphId="e_296_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3838.0" Y="269.0" GraphId="e_296_o1_0" ArrowHead="Arrow" GraphRef="n232_REACTOME_31633" RelX="0.3333333333333333" RelY="-1.1612903225806452"/> <Point X="3870.0" Y="216.0" GraphId="e_296_o1_1" GraphRef="e_296_a_o"/> </Graphics> </Line> <Line GraphId="e_296_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3851.0" Y="158.0" GraphId="e_296_c__0_0" GraphRef="n139_REACTOME_444422" RelX="1.1627906976744187" RelY="0.0"/> <Point X="3870.0" Y="160.0" GraphId="e_296_c__0_1" GraphRef="e_296_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_297_REACTOME_446277"> <Comment Source="WikiPathways-description">The human gene RhCG encodes the Rhesus blood group family type C glycoprotein which is mainly expressed in kidney collecting duct but also found in testis. RhCG is located on the apical membrane and mediates the bi-directional transport of ammonium into and out of renal collecting duct cells in an electroneutral manner, with H+ transported the other way (Liu Z et al, 2000; Marini AM et al, 2000).</Comment> <BiopaxRef>lit_444415</BiopaxRef> <BiopaxRef>lit_444394</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3953.0" Y="219.0" GraphId="e_297_0"/> <Point X="3953.0" Y="159.0" GraphId="e_297_1"/> <Point X="3953.0" Y="92.0" GraphId="e_297_2"/> <Anchor Position="0.0" GraphId="e_297_a_i"/> <Anchor Position="0.47244094488188976" GraphId="e_297_a_p"/> <Anchor Position="1.0" GraphId="e_297_a_o"/> </Graphics> </Line> <Line GraphId="e_297_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3992.0" Y="274.0" GraphId="e_297_i0_0" GraphRef="n140_REACTOME_31633" RelX="-0.4583333333333333" RelY="-1.1612903225806452"/> <Point X="3953.0" Y="219.0" GraphId="e_297_i0_1" GraphRef="e_297_a_i"/> </Graphics> </Line> <Line GraphId="e_297_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3952.0" Y="76.0" GraphId="e_297_i1_0" GraphRef="n235_REACTOME_351626" RelX="0.0" RelY="1.2258064516129032"/> <Point X="3953.0" Y="219.0" GraphId="e_297_i1_1" GraphRef="e_297_a_i"/> </Graphics> </Line> <Line GraphId="e_297_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3986.0" Y="44.0" GraphId="e_297_o0_0" ArrowHead="Arrow" GraphRef="n137_REACTOME_140912" RelX="-0.4583333333333333" RelY="1.2258064516129032"/> <Point X="3953.0" Y="92.0" GraphId="e_297_o0_1" GraphRef="e_297_a_o"/> </Graphics> </Line> <Line GraphId="e_297_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="3952.0" Y="252.0" GraphId="e_297_o1_0" ArrowHead="Arrow" GraphRef="n236_REACTOME_70106" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="3953.0" Y="92.0" GraphId="e_297_o1_1" GraphRef="e_297_a_o"/> </Graphics> </Line> <Line GraphId="e_297_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="3973.0" Y="159.0" GraphId="e_297_c__0_0" GraphRef="n138_REACTOME_444397" RelX="-1.1363636363636365" RelY="-0.08695652173913043"/> <Point X="3953.0" Y="159.0" GraphId="e_297_c__0_1" GraphRef="e_297_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_310_REACTOME_561059"> <Comment Source="WikiPathways-description">The human gene SLC22A7 encodes organic anion transporter 2 (OAT2) and is highly expressed in the liver and kidney (Sun W et al, 2001; Kobayashi Y et al, 2005). The human gene SLC22A11 encodes organic anion transporter 4 (OAT4) which is highly expressed in the placenta and kidney (Cha SH et al, 2000; Ekaratanawong S et al, 2004). Both of these transporters mediate the influx of sulfate conjugates with antiport of dicarboxylic acid. OAT2 is classified as both a transporter of organic anions and sulphate conjugates.</Comment> <BiopaxRef>lit_561060</BiopaxRef> <BiopaxRef>lit_561086</BiopaxRef> <BiopaxRef>lit_561248</BiopaxRef> <BiopaxRef>lit_561246</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4923.0" Y="112.0" GraphId="e_310_0"/> <Point X="4922.0" Y="158.0" GraphId="e_310_1"/> <Point X="4922.0" Y="214.0" GraphId="e_310_2"/> <Anchor Position="0.0" GraphId="e_310_a_i"/> <Anchor Position="0.4510388849394743" GraphId="e_310_a_p"/> <Anchor Position="1.0" GraphId="e_310_a_o"/> </Graphics> </Line> <Line GraphId="e_310_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4923.0" Y="87.0" GraphId="e_310_i0_0" GraphRef="n301_REACTOME_561071" RelX="0.0" RelY="1.1304347826086956"/> <Point X="4923.0" Y="112.0" GraphId="e_310_i0_1" GraphRef="e_310_a_i"/> </Graphics> </Line> <Line GraphId="e_310_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4979.0" Y="214.0" GraphId="e_310_i1_0" GraphRef="n302_REACTOME_29406" RelX="-1.0638297872340425" RelY="-0.7096774193548387"/> <Point X="4922.0" Y="201.0" GraphId="e_310_i1_1"/> <Point X="4923.0" Y="112.0" GraphId="e_310_i1_2" GraphRef="e_310_a_i"/> </Graphics> </Line> <Line GraphId="e_310_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4922.0" Y="240.0" GraphId="e_310_o0_0" ArrowHead="Arrow" GraphRef="n300_REACTOME_561062" RelX="0.0" RelY="-1.1304347826086956"/> <Point X="4922.0" Y="214.0" GraphId="e_310_o0_1" GraphRef="e_310_a_o"/> </Graphics> </Line> <Line GraphId="e_310_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4980.0" Y="103.0" GraphId="e_310_o1_0" ArrowHead="Arrow" GraphRef="n307_REACTOME_561075" RelX="-1.0625" RelY="0.9032258064516129"/> <Point X="4924.0" Y="122.0" GraphId="e_310_o1_1"/> <Point X="4922.0" Y="214.0" GraphId="e_310_o1_2" GraphRef="e_310_a_o"/> </Graphics> </Line> <Line GraphId="e_310_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4943.0" Y="157.0" GraphId="e_310_c__0_0" GraphRef="n304_REACTOME_561077" RelX="-1.125" RelY="0.0"/> <Point X="4922.0" Y="158.0" GraphId="e_310_c__0_1" GraphRef="e_310_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_311_REACTOME_561253"> <Comment Source="WikiPathways-description">Urate is a naturally occurring product of purine metabolism and is a scavenger of biological oxidants. Due to this ability, changes in urate levels are implicated in numerous disease processes. The human gene SLC22A12 encodes urate transporter 1 (URAT1), predominantly expressed in the kidney and is involved in the regulation of blood urate levels. This transport can be trans-stimulated by organic anions such as L-lactate (Enomoto A et al, 2002). Defects in SLC22A12 result in idiopathic renal hypouricaemia (lack of blood urate) (Wakida N et al, 2005).</Comment> <BiopaxRef>lit_561226</BiopaxRef> <BiopaxRef>lit_561250</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4739.0" Y="123.0" GraphId="e_311_0"/> <Point X="4740.0" Y="160.0" GraphId="e_311_1"/> <Point X="4741.0" Y="158.0" GraphId="e_311_2"/> <Anchor Position="0.0" GraphId="e_311_a_i"/> <Anchor Position="0.9430295041859089" GraphId="e_311_a_p"/> <Anchor Position="1.0" GraphId="e_311_a_o"/> </Graphics> </Line> <Line GraphId="e_311_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4775.0" Y="98.0" GraphId="e_311_i0_0" GraphRef="n298_REACTOME_429056" RelX="-0.8695652173913043" RelY="1.2258064516129032"/> <Point X="4739.0" Y="123.0" GraphId="e_311_i0_1" GraphRef="e_311_a_i"/> </Graphics> </Line> <Line GraphId="e_311_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4741.0" Y="227.0" GraphId="e_311_i1_0" GraphRef="n313_REACTOME_29708" RelX="-0.02631578947368421" RelY="-1.1612903225806452"/> <Point X="4739.0" Y="123.0" GraphId="e_311_i1_1" GraphRef="e_311_a_i"/> </Graphics> </Line> <Line GraphId="e_311_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4741.0" Y="54.0" GraphId="e_311_o0_0" ArrowHead="Arrow" GraphRef="n305_REACTOME_373863" RelX="-0.02631578947368421" RelY="1.2258064516129032"/> <Point X="4741.0" Y="158.0" GraphId="e_311_o0_1" GraphRef="e_311_a_o"/> </Graphics> </Line> <Line GraphId="e_311_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4788.0" Y="190.0" GraphId="e_311_o1_0" ArrowHead="Arrow" GraphRef="n306_REACTOME_30034" RelX="-0.9565217391304348" RelY="-1.1612903225806452"/> <Point X="4741.0" Y="158.0" GraphId="e_311_o1_1" GraphRef="e_311_a_o"/> </Graphics> </Line> <Line GraphId="e_311_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4719.0" Y="160.0" GraphId="e_311_c__0_0" GraphRef="n299_REACTOME_561098" RelX="1.148936170212766" RelY="0.0"/> <Point X="4740.0" Y="160.0" GraphId="e_311_c__0_1" GraphRef="e_311_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_312_REACTOME_561041"> <Comment Source="WikiPathways-description">The human gene SLC22A6 encodes organic anion transporter1 (OAT1). It was originally characterized in mouse as Novel Kidney Transcript (NKT). OAT1 is located on the basolateral membrane of the proximal tubule in human kidney as well as in the brain (Reid G et al, 1998; Lu R et al, 1999; Hosoyamada M et al, 1999). The human gene SLC22A7 encodes organic anion transporter 2 (OAT2) and is highly expressed in the liver and kidney (Sun W et al, 2001; Kobayashi Y et al, 2005). The human gene SLC22A8 encodes organic anion transporter 3 (OAT3) which is expressed mainly in the brain and kidney (Race JE et al, 1999; Bakhiya A et al, 2003). &lt;br&gt;OAT1-3 transport organic anions such as p-aminohippurate and drugs such as cimetidine and acyclovir. This transport is is coupled with an efflux of one molecule of endogenous dicarboxylic acid such as alpha-ketoglutarate (2-oxoglutarate). OAT2 is classified as both a transporter of organic anions and sulphate conjugates.</Comment> <BiopaxRef>lit_561080</BiopaxRef> <BiopaxRef>lit_561051</BiopaxRef> <BiopaxRef>lit_561245</BiopaxRef> <BiopaxRef>lit_561248</BiopaxRef> <BiopaxRef>lit_561060</BiopaxRef> <BiopaxRef>lit_561045</BiopaxRef> <BiopaxRef>lit_561040</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5120.0" Y="87.0" GraphId="e_312_0"/> <Point X="5120.0" Y="157.0" GraphId="e_312_1"/> <Point X="5121.0" Y="214.0" GraphId="e_312_2"/> <Anchor Position="0.0" GraphId="e_312_a_i"/> <Anchor Position="0.5511430376684952" GraphId="e_312_a_p"/> <Anchor Position="1.0" GraphId="e_312_a_o"/> </Graphics> </Line> <Line GraphId="e_312_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5076.0" Y="207.0" GraphId="e_312_i0_0" GraphRef="n302_REACTOME_29406" RelX="1.0" RelY="-1.1612903225806452"/> <Point X="5120.0" Y="195.0" GraphId="e_312_i0_1"/> <Point X="5120.0" Y="87.0" GraphId="e_312_i0_2" GraphRef="e_312_a_i"/> </Graphics> </Line> <Line GraphId="e_312_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5121.0" Y="73.0" GraphId="e_312_i1_0" GraphRef="n303_REACTOME_561049" RelX="-0.01680672268907563" RelY="1.2258064516129032"/> <Point X="5120.0" Y="87.0" GraphId="e_312_i1_1" GraphRef="e_312_a_i"/> </Graphics> </Line> <Line GraphId="e_312_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5082.0" Y="103.0" GraphId="e_312_o0_0" ArrowHead="Arrow" GraphRef="n307_REACTOME_561075" RelX="1.0625" RelY="0.9032258064516129"/> <Point X="5119.0" Y="115.0" GraphId="e_312_o0_1"/> <Point X="5121.0" Y="214.0" GraphId="e_312_o0_2" GraphRef="e_312_a_o"/> </Graphics> </Line> <Line GraphId="e_312_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5121.0" Y="241.0" GraphId="e_312_o1_0" ArrowHead="Arrow" GraphRef="n308_REACTOME_561078" RelX="0.0" RelY="-1.1612903225806452"/> <Point X="5121.0" Y="214.0" GraphId="e_312_o1_1" GraphRef="e_312_a_o"/> </Graphics> </Line> <Line GraphId="e_312_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="5096.0" Y="157.0" GraphId="e_312_c__0_0" GraphRef="n309_REACTOME_561087" RelX="1.1428571428571428" RelY="-0.08695652173913043"/> <Point X="5120.0" Y="157.0" GraphId="e_312_c__0_1" GraphRef="e_312_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_336_REACTOME_549297"> <Comment Source="WikiPathways-description">The human gene SLC22A5 encodes the organic cation/carnitine transporter 2 (OCTN2). OCTN2 is strongly expressed in the kidney, skeletal muscle, heart and placenta (Tamai I et al, 1998). Defects in SLC22A5 are the cause of systemic primary carnitine deficiency (CDSP) (Tang NL et al, 1999) and susceptibility to Crohn disease (CD) (Peltekova VD et al, 2004). The human gene SLC22A15 encodes the fly-like putative transporter1 (FLIPT1). FLIPT1 is a novel transporter highly expressed in kidney and brain is shown to be homologous to other carnitine transporters (Eraly SA and Nigan SK, 2002). The human gene SLC22A16 encodes the organic cation/carnitine transporter 6 (also called the fly-like putative transporter 2, FLIPT2) (Enomoto A et al, 2002). FLIPT2 is strongly expressed in the testis and epididymas as well as generally in other tissues and in leukaemia cells ( Enomoto A et al, 2002; Gong S et al, 2002). All of these transporters are sodium-dependent, high affinity carnitine cotransporters.</Comment> <BiopaxRef>lit_549323</BiopaxRef> <BiopaxRef>lit_549253</BiopaxRef> <BiopaxRef>lit_549300</BiopaxRef> <BiopaxRef>lit_597632</BiopaxRef> <BiopaxRef>lit_597599</BiopaxRef> <BiopaxRef>lit_706445</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5335.0" Y="114.0" GraphId="e_336_0"/> <Point X="5335.0" Y="158.0" GraphId="e_336_1"/> <Point X="5335.0" Y="308.0" GraphId="e_336_2"/> <Anchor Position="0.0" GraphId="e_336_a_i"/> <Anchor Position="0.2268041237113402" GraphId="e_336_a_p"/> <Anchor Position="1.0" GraphId="e_336_a_o"/> </Graphics> </Line> <Line GraphId="e_336_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5389.0" Y="92.0" GraphId="e_336_i0_0" GraphRef="n330_REACTOME_74113" RelX="-1.0769230769230769" RelY="0.9032258064516129"/> <Point X="5335.0" Y="114.0" GraphId="e_336_i0_1" GraphRef="e_336_a_i"/> </Graphics> </Line> <Line GraphId="e_336_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5301.0" Y="96.0" GraphId="e_336_i1_0" GraphRef="n334_REACTOME_164988" RelX="0.7272727272727273" RelY="1.2258064516129032"/> <Point X="5335.0" Y="114.0" GraphId="e_336_i1_1" GraphRef="e_336_a_i"/> </Graphics> </Line> <Line GraphId="e_336_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5294.0" Y="327.0" GraphId="e_336_o0_0" ArrowHead="Arrow" GraphRef="n318_REACTOME_30235" RelX="0.8484848484848485" RelY="-1.1612903225806452"/> <Point X="5335.0" Y="308.0" GraphId="e_336_o0_1" GraphRef="e_336_a_o"/> </Graphics> </Line> <Line GraphId="e_336_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5394.0" Y="329.0" GraphId="e_336_o1_0" ArrowHead="Arrow" GraphRef="n321_REACTOME_83910" RelX="-1.0256410256410255" RelY="-1.1612903225806452"/> <Point X="5335.0" Y="308.0" GraphId="e_336_o1_1" GraphRef="e_336_a_o"/> </Graphics> </Line> <Line GraphId="e_336_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="5311.0" Y="159.0" GraphId="e_336_c__0_0" GraphRef="n315_REACTOME_597614" RelX="1.046875" RelY="-0.2608695652173913"/> <Point X="5335.0" Y="158.0" GraphId="e_336_c__0_1" GraphRef="e_336_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_337_REACTOME_549241"> <Comment Source="WikiPathways-description">The human gene SLC22A4 encodes the ergothioneine transporter (ETT). It was originally discovered as a organic cation/carnitine transporter (OCTN1) (Tamai I et al, 1997) but its main substrate is not carnitine. It is widely expressed and transports ergothioneine more than 100 times more efficiently than tetraethylammonium and carnitine (Grundemann D et al, 2005), leading to the name change from OCTN1 to ETT. Defects in SLC22A4 may be a cause of susceptibility to Crohn disease (CD) (Peltekova VD et al, 2004).</Comment> <BiopaxRef>lit_549265</BiopaxRef> <BiopaxRef>lit_549300</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5518.0" Y="115.0" GraphId="e_337_0"/> <Point X="5518.0" Y="158.0" GraphId="e_337_1"/> <Point X="5518.0" Y="286.0" GraphId="e_337_2"/> <Anchor Position="0.0" GraphId="e_337_a_i"/> <Anchor Position="0.25146198830409355" GraphId="e_337_a_p"/> <Anchor Position="1.0" GraphId="e_337_a_o"/> </Graphics> </Line> <Line GraphId="e_337_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5556.0" Y="91.0" GraphId="e_337_i0_0" GraphRef="n314_REACTOME_549261" RelX="-0.4731182795698925" RelY="1.2258064516129032"/> <Point X="5518.0" Y="115.0" GraphId="e_337_i0_1" GraphRef="e_337_a_i"/> </Graphics> </Line> <Line GraphId="e_337_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5467.0" Y="97.0" GraphId="e_337_i1_0" GraphRef="n330_REACTOME_74113" RelX="0.9230769230769231" RelY="1.2258064516129032"/> <Point X="5518.0" Y="115.0" GraphId="e_337_i1_1" GraphRef="e_337_a_i"/> </Graphics> </Line> <Line GraphId="e_337_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5566.0" Y="334.0" GraphId="e_337_o0_0" ArrowHead="Arrow" GraphRef="n327_REACTOME_549260" RelX="-0.3225806451612903" RelY="-1.1612903225806452"/> <Point X="5518.0" Y="286.0" GraphId="e_337_o0_1" GraphRef="e_337_a_o"/> </Graphics> </Line> <Line GraphId="e_337_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5455.0" Y="329.0" GraphId="e_337_o1_0" ArrowHead="Arrow" GraphRef="n321_REACTOME_83910" RelX="0.5384615384615384" RelY="-1.1612903225806452"/> <Point X="5518.0" Y="286.0" GraphId="e_337_o1_1" GraphRef="e_337_a_o"/> </Graphics> </Line> <Line GraphId="e_337_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="5473.0" Y="161.0" GraphId="e_337_c__0_0" GraphRef="n332_REACTOME_549252" RelX="1.2" RelY="-0.17391304347826086"/> <Point X="5518.0" Y="158.0" GraphId="e_337_c__0_1" GraphRef="e_337_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_338_REACTOME_549304"> <Comment Source="WikiPathways-description">The human gene SLC22A3 encodes organic cation transporter OCT3. It is mainly expressed in skeletal muscle, liver, placenta, kidney and heart, and to a lesser extent in brain. OCT3 is involved in the biliary excretion of cationic drugs. In CNS, ganglia and heart, OCT3 regulates the interstitial concentrations of monoamine neurotransmitters and cationic drugs. In placenta, OCT3 is responsible for the release of acetylcholine during nonneuronal cholinergic regulation (Grundemann D et al,1998; Wu X et al, 2000).</Comment> <BiopaxRef>lit_549283</BiopaxRef> <BiopaxRef>lit_549238</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5149.0" Y="782.0" GraphId="e_338_0" GraphRef="n335_REACTOME_549326" RelX="0.0" RelY="1.2258064516129032"/> <Point X="5149.0" Y="828.0" GraphId="e_338_1"/> <Point X="5149.0" Y="891.0" GraphId="e_338_2" GraphRef="n320_REACTOME_549255" RelX="-0.01818181818181818" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.42201834862385323" GraphId="e_338_a_p"/> </Graphics> </Line> <Line GraphId="e_338_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="5135.0" Y="828.0" GraphId="e_338_c__0_0" GraphRef="n329_REACTOME_549257" RelX="1.15" RelY="0.0"/> <Point X="5149.0" Y="828.0" GraphId="e_338_c__0_1" GraphRef="e_338_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_339_REACTOME_549279"> <Comment Source="WikiPathways-description">The human gene SLC22A2 encodes the organic cation transporter OCT2. It is expressed in a variety of tissues, especially the kidney and placenta. OCT2 can mediate the reversible transport of a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (Gorboulev V et al, 1997). Pharmaceuticals that up-regulate OCT2 in the kidney can increase the renal excretion of cationic drugs.</Comment> <BiopaxRef>lit_549290</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4885.0" Y="881.0" GraphId="e_339_0" GraphRef="n319_REACTOME_549237" RelX="-0.01818181818181818" RelY="-1.1612903225806452"/> <Point X="4885.0" Y="828.0" GraphId="e_339_1"/> <Point X="4885.0" Y="776.0" GraphId="e_339_2" GraphRef="n325_REACTOME_549266" RelX="0.0" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.5047619047619047" GraphId="e_339_a_p"/> </Graphics> </Line> <Line GraphId="e_339_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4911.0" Y="827.0" GraphId="e_339_c__0_0" GraphRef="n326_REACTOME_374914" RelX="-1.0461538461538462" RelY="0.0"/> <Point X="4885.0" Y="828.0" GraphId="e_339_c__0_1" GraphRef="e_339_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_340_REACTOME_549129"> <Comment Source="WikiPathways-description">The human gene SLC22A1 expresses the organic cation transporter 1 (OCT1) mainly in the liver. It can mediate the reversible transport of a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (Zhang L et al, 1998; Gorboulev V et al, 1997).</Comment> <BiopaxRef>lit_549318</BiopaxRef> <BiopaxRef>lit_549290</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4743.0" Y="891.0" GraphId="e_340_0" GraphRef="n322_REACTOME_549264" RelX="-0.01818181818181818" RelY="-1.1612903225806452"/> <Point X="4742.0" Y="831.0" GraphId="e_340_1"/> <Point X="4741.0" Y="764.0" GraphId="e_340_2" GraphRef="n317_REACTOME_549250" RelX="0.0" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.4724477986581241" GraphId="e_340_a_p"/> </Graphics> </Line> <Line GraphId="e_340_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4727.0" Y="831.0" GraphId="e_340_c__0_0" GraphRef="n323_REACTOME_549126" RelX="1.15" RelY="0.0"/> <Point X="4742.0" Y="831.0" GraphId="e_340_c__0_1" GraphRef="e_340_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_341_REACTOME_597628"> <Comment Source="WikiPathways-description">The human gene SLC22A18 encodes organic cation transporter-like protein 2 (ORCTL2). It is expressed to high levels in kidney, liver and colon. ORCTL2 can transport chloroquine and quinidine with the antiport of protons (Reece M et al, 1998). Defects in SLC22A18 may play a role in tumorigenesis (Schwienbacher C et al, 1998).</Comment> <BiopaxRef>lit_597616</BiopaxRef> <BiopaxRef>lit_597602</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5354.0" Y="774.0" GraphId="e_341_0"/> <Point X="5353.0" Y="827.0" GraphId="e_341_1"/> <Point X="5354.0" Y="859.0" GraphId="e_341_2"/> <Anchor Position="0.0" GraphId="e_341_a_i"/> <Anchor Position="0.623456621733502" GraphId="e_341_a_p"/> <Anchor Position="1.0" GraphId="e_341_a_o"/> </Graphics> </Line> <Line GraphId="e_341_i0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5354.0" Y="907.0" GraphId="e_341_i0_0" GraphRef="n333_REACTOME_597604" RelX="-0.015873015873015872" RelY="-1.1612903225806452"/> <Point X="5354.0" Y="774.0" GraphId="e_341_i0_1" GraphRef="e_341_a_i"/> </Graphics> </Line> <Line GraphId="e_341_i1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5408.0" Y="756.0" GraphId="e_341_i1_0" GraphRef="n328_REACTOME_70106" RelX="-1.1875" RelY="0.3225806451612903"/> <Point X="5354.0" Y="774.0" GraphId="e_341_i1_1" GraphRef="e_341_a_i"/> </Graphics> </Line> <Line GraphId="e_341_o0"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5355.0" Y="732.0" GraphId="e_341_o0_0" ArrowHead="Arrow" GraphRef="n324_REACTOME_597623" RelX="-0.015873015873015872" RelY="1.2258064516129032"/> <Point X="5354.0" Y="859.0" GraphId="e_341_o0_1" GraphRef="e_341_a_o"/> </Graphics> </Line> <Line GraphId="e_341_o1"> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5418.0" Y="879.0" GraphId="e_341_o1_0" ArrowHead="Arrow" GraphRef="n316_REACTOME_351626" RelX="-1.1875" RelY="-0.3870967741935484"/> <Point X="5354.0" Y="859.0" GraphId="e_341_o1_1" GraphRef="e_341_a_o"/> </Graphics> </Line> <Line GraphId="e_341_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="5313.0" Y="829.0" GraphId="e_341_c__0_0" GraphRef="n331_REACTOME_561110" RelX="1.1071428571428572" RelY="-0.17391304347826086"/> <Point X="5353.0" Y="827.0" GraphId="e_341_c__0_1" GraphRef="e_341_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_428_REACTOME_549322"> <Comment Source="WikiPathways-description">The human gene SLC22A1 expresses the organic cation transporter 1 (OCT1) mainly in the liver. It can mediate the reversible transport of a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (Zhang L et al, 1998; Gorboulev V et al, 1997).</Comment> <BiopaxRef>lit_549318</BiopaxRef> <BiopaxRef>lit_549290</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4741.0" Y="764.0" GraphId="e_428_0" GraphRef="n317_REACTOME_549250" RelX="0.0" RelY="1.2258064516129032"/> <Point X="4741.0" Y="831.0" GraphId="e_428_1"/> <Point X="4743.0" Y="891.0" GraphId="e_428_2" GraphRef="n322_REACTOME_549264" RelX="-0.01818181818181818" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.5274206629295208" GraphId="e_428_a_p"/> </Graphics> </Line> <Line GraphId="e_428_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4727.0" Y="831.0" GraphId="e_428_c__0_0" GraphRef="n323_REACTOME_549126" RelX="1.15" RelY="0.0"/> <Point X="4741.0" Y="831.0" GraphId="e_428_c__0_1" GraphRef="e_428_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_436_REACTOME_561054"> <Comment Source="WikiPathways-description">The human gene SLC22A2 encodes the organic cation transporter OCT2. It is expressed in a variety of tissues, especially the kidney and placenta. OCT2 can mediate the reversible transport of a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (Gorboulev V et al, 1997). Pharmaceuticals that up-regulate OCT2 in the kidney can increase the renal excretion of cationic drugs.</Comment> <BiopaxRef>lit_374923</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="4885.0" Y="776.0" GraphId="e_436_0" GraphRef="n325_REACTOME_549266" RelX="0.0" RelY="1.2258064516129032"/> <Point X="4885.0" Y="828.0" GraphId="e_436_1"/> <Point X="4885.0" Y="881.0" GraphId="e_436_2" GraphRef="n319_REACTOME_549237" RelX="-0.01818181818181818" RelY="-1.1612903225806452" ArrowHead="Arrow"/> <Anchor Position="0.49523809523809526" GraphId="e_436_a_p"/> </Graphics> </Line> <Line GraphId="e_436_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="4911.0" Y="827.0" GraphId="e_436_c__0_0" GraphRef="n438_REACTOME_374914" RelX="-1.0461538461538462" RelY="0.0"/> <Point X="4885.0" Y="828.0" GraphId="e_436_c__0_1" GraphRef="e_436_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_446_REACTOME_561072"> <Comment Source="WikiPathways-description">The human gene SLC22A3 encodes organic cation transporter OCT3. It is mainly expressed in skeletal muscle, liver, placenta, kidney and heart, and to a lesser extent in brain. OCT3 is involved in the biliary excretion of cationic drugs. In CNS, ganglia and heart, OCT3 regulates the interstitial concentrations of monoamine neurotransmitters and cationic drugs. In placenta, OCT3 is responsible for the release of acetylcholine during nonneuronal cholinergic regulation (Grundemann D et al,1998; Wu X et al, 2000).</Comment> <BiopaxRef>lit_549283</BiopaxRef> <BiopaxRef>lit_549238</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="5149.0" Y="891.0" GraphId="e_446_0" GraphRef="n320_REACTOME_549255" RelX="-0.01818181818181818" RelY="-1.1612903225806452"/> <Point X="5149.0" Y="829.0" GraphId="e_446_1"/> <Point X="5149.0" Y="782.0" GraphId="e_446_2" GraphRef="n335_REACTOME_549326" RelX="0.0" RelY="1.2258064516129032" ArrowHead="Arrow"/> <Anchor Position="0.5688073394495413" GraphId="e_446_a_p"/> </Graphics> </Line> <Line GraphId="e_446_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="5135.0" Y="828.0" GraphId="e_446_c__0_0" GraphRef="n329_REACTOME_549257" RelX="1.15" RelY="0.0"/> <Point X="5149.0" Y="829.0" GraphId="e_446_c__0_1" GraphRef="e_446_a_p" ArrowHead="Line"/> </Graphics> </Line> <Line GraphId="e_450_REACTOME_904830"> <Comment Source="WikiPathways-description">MTP1 is also highly expressed on macrophages where it mediates iron efflux from the breakdown of haem.&lt;br&gt;The human gene SLC40A1 encodes a metal transporter protein MTP1 (also called ferroportin or IREG1) (Schimanski LM et al, 2005). MTP1 colocalizes with ceruloplasmin (CP) which stablizes MTP1 and is necessary for the efflux reaction to occur (Texel SJ et al, 2008). Ceruloplasmin also catalyzes the conversion of iron from ferrous (Fe2+) to ferric form (Fe3+), therefore assisting in its transport in the plasma in association with transferrin, which can only carry iron in the ferric state. As well as on macrophages, MTP1 is also highly expressed in the duodenum, placenta (where it may mediate the transport of iron from maternal to foetal circulation), in muscle and the spleen.</Comment> <BiopaxRef>lit_904841</BiopaxRef> <BiopaxRef>lit_442331</BiopaxRef> <Graphics LineStyle="Solid" Color="000000" ConnectorType="Segmented"> <Point X="2386.0" Y="52.0" GraphId="e_450_0" GraphRef="n38_REACTOME_71067" RelX="1.0804597701149425" RelY="-0.06451612903225806"/> <Point X="2451.0" Y="52.0" GraphId="e_450_1"/> <Point X="2451.0" Y="157.0" GraphId="e_450_2"/> <Point X="2451.0" Y="254.0" GraphId="e_450_3"/> <Point X="2387.0" Y="254.0" GraphId="e_450_4" GraphRef="n39_REACTOME_435347" RelX="1.0804597701149425" RelY="0.0" ArrowHead="Arrow"/> <Anchor Position="0.513595166163142" GraphId="e_450_a_p"/> </Graphics> </Line> <Line GraphId="e_450_c__0"> <Graphics LineStyle="Broken" Color="000000" ConnectorType="Segmented"> <Point X="2466.0" Y="156.0" GraphId="e_450_c__0_0" 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Valign="Middle" FontSize="12"/> </Label> <Label GraphId="comp_text_225" GroupRef="group_comp_225" TextLabel="Golgi lumen"> <Graphics Color="000000" CenterX="405.0" CenterY="759.5" Width="88.0" Height="33.0" Valign="Middle" FontSize="12"/> </Label> <Label GraphId="comp_text_226" GroupRef="group_comp_226" TextLabel="endoplasmic reticulum lumen"> <Graphics Color="000000" CenterX="844.0" CenterY="513.5" Width="154.0" Height="47.0" Valign="Middle" FontSize="12"/> </Label> <Label GraphId="comp_text_227" GroupRef="group_comp_227" TextLabel="clathrin sculpted monoamine transport vesicle lumen"> <Graphics Color="000000" CenterX="1318.5" CenterY="366.5" Width="247.0" Height="47.0" Valign="Middle" FontSize="12"/> </Label> <Label GraphId="comp_text_228" GroupRef="group_comp_228" TextLabel="late endosome lumen"> <Graphics Color="000000" CenterX="1883.0" CenterY="316.5" Width="144.0" Height="33.0" Valign="Middle" FontSize="12"/> </Label> <Shape GraphId="comp_221" GroupRef="group_comp_221"> <Graphics 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pubmed</bp:DB> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#int">2009</bp:YEAR> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Analysis and update of the human solute carrier (SLC) gene superfamily</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">He, L</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Vasiliou, K</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Nebert, DW</bp:AUTHORS> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Hum Genomics 3:195-206</bp:SOURCE> </bp:publicationXref> <bp:publicationXref xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" rdf:ID="lit_428756" rdf:id="lit_428756"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">12750891</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pubmed</bp:DB> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#int">2004</bp:YEAR> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">The SLC2 family of facilitated hexose and polyol transporters</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Uldry, M</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Thorens, B</bp:AUTHORS> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pflugers Arch 447:480-9</bp:SOURCE> </bp:publicationXref> <bp:publicationXref xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" rdf:ID="lit_428758" rdf:id="lit_428758"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">12748858</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pubmed</bp:DB> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#int">2004</bp:YEAR> 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<bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Ceruloplasmin in neurodegenerative diseases</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Texel, SJ</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Xu, X</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Harris, ZL</bp:AUTHORS> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Biochem Soc Trans 36:1277-81</bp:SOURCE> </bp:publicationXref> <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#"><bp:TERM>sugar transport pathway</bp:TERM><bp:ID>PW:0000575</bp:ID><bp:Ontology>Pathway Ontology</bp:Ontology></bp:openControlledVocabulary></Biopax> </Pathway>

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