Expression cloning and characterization of a novel. A human canalicular multispecific organic anion transporter cmoat gene is overexpressed in cisplatinresistant human cancer cell lines with decreased drug accumulation. Recently, renal adverse effects of cisplatin were demonstrated to be. Experiments with human embryonic kidney293 cells stably transfected with human oat1, oat2, or oat3 were performed to compare selected transport properties. Imagine a global collaborative knowledge base for original thoughts. What is canicular multispecific organic anion transporter. Multispecific organic anion transport carriers are present. Organic anion transporter 4 organic anion transporters. Hiroyuki kusuhara, yuichi sugiyama, involvement of multispecific organic anion transporter, oatp14 slc21a14, in the transport of thyroxine across the bloodbrain barrier. Transporters oat1 organic anion transporter 1 slc22a6 c show summary hide summary more detailed page. In chronic cholangitis only canalicular mrp2 expression remained downregulated. Organic anion transporters play important roles in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body. The amino acid sequence of nlt shows 42% identity to that of the renal multispecific organic anion transporter, oat1. The role of the canalicular multispecific organic anion.
Jan 19, 2016 what does organic anion transporters mean in english. This protein is expressed in the canalicular apical part of the hepatocyte and. Canalicular multispecific organic anion transporter 1 ipr030247. Mediates hepatobiliary excretion of numerous organic anions and conjugated organic anions such as methotrexate, 17betaestradiol 17glucosiduronic acid and leukotriene c4 pubmed. A canalicular multispecific organic anion transporter cmoat antisense cdna enhances drug sensitivity in human hepatic cancer cells. Identification of multispecific organic anion transporter 2. This entry represents canalicular multispecific organic anion transporter 1 also known as mrp2 or abcc2 from animals. Solute carrier family 22 member 68 slc22a68 summary. Pglycoprotein and multidrug resistance associated protein extrude a range of anticancer. Mediates hepatobiliary excretion of numerous organic anions and conjugated organic anions such as methotrexate, 17betaestradiol 17glucosiduronic acid and leukotriene c4.
A canalicular multispecific organic anion transporter cmoat ncbi. Several families of multispecific organic anion and cation transporters, including oat family transporters, have recently been identified by molecular cloning. The multispecific organic anion transporter oat family. Pdf canalicular multispecific organic anion transporter. The canalicular multispecific organic anion transporter and. Effect of multidrug resistancereversing agents on transporting activity of human canalicular multispecific organic anion transporter. A cdna encoding a multispecific organic anion transporter 3 hoat3 was isolated from a human kidney cdna library. The canalicular multispecific organic anion transporter, cmoat, is an atpbindingcassette protein. Pdf on oct 1, 2008, hiremagalur n jayaram and others published can targeting organic anion transporter polypeptide oatp genes play a key role in drug therapy. How is canalicular multispecific organic anion transporter abbreviated. Involvement of multispecific organic anion transporter, oatp14 slc21a14. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes by similarity. Organic anion transporter 1 an overview sciencedirect topics. Multispecific organic anion transport carriers are present in the a.
Human organic anion transporter 1 oat1 encodes a 563 amino acid residue protein, and which is predicted 12 putative membranespanning protein. Drug export activity of the human canalicular multispecific. Looking for online definition of canicular multispecific organic anion transporter in the medical dictionary. Showing protein canalicular multispecific organic anion. Abstract phylogentically, organic anion transporter oat1 and oat3 are closely related, whereas oat2 is more distant. Molecular cloning and characterization of multispecific. Canalicular multispecific organic anion transporter 1 atpbinding cassette subfamily c member 2 canalicular multidrug resistance protein multidrug resistanceassociated protein 2, ec 7. Oct1 is primarily a hepatic uptake transporter, expressed on the sinusoidal membrane blood side of hepatocytes. A similar fragment is also conserved in some odorant receptors ors in both humans and rodents. It plays a key role in the disposition and hepatic clearance of mostly cationic drugs and endogenous compounds. Organic anion transporters oats transporters iupharbps. Patients have impaired hepatobiliary transport of many endogenous and xenobiotic compounds. In type 2 diabetes, polymorphisms associated with altered metformin response have been identified in the solute carrier family 22 organic cation transporter, member 1 slc22a1, and solute carrier family 22 organic cation transporter, member 2 slc22a2, genes encoding the organic cation transporter 1 and 2 proteins, oct1 and oct2, respectively and the solute carrier family 47, member 1. Protein ontology mediates hepatobiliary excretion of numerous organic anions and conjugated organic anions such as methotrexate, 17betaestradiol 17glucosiduronic acid and leukotriene c4 pmid.
Mrp1, the founding member of the subfamily, was identified as the basis for drug resistance. Organic anion transporter polypeptide 1b1 polymorphism modulates the extent of drugdrug interaction and associated biomarker levels in healthy volunteers. Organic anion transporter 3 contributes to the regulation. Mrp2abcc2, previously known as canalicular multispecific organic anion transporter 1 cmoat1 paulusma et al.
Canalicular multispecific organic anion transporter 1 uniprot. Cloning of the fulllength coding sequence of rat liverspecific organic anion transporter1 rlst1 and a. What does organic anion transporters mean in english. Watch live impeachment trial of president donald trump day four. Human 8, 9 and mouse 10, 11 homolog have been also cloned and characterized. Description this entry represents canalicular multispecific organic anion transporter 1 also known as mrp2 or abcc2 from animals. Organic anion transporter 1 oat1, slc22a6 and 3 oat3, slc22a8 in proximal tubule cells play a main role in clearance of organic anions, including endogenous uremic toxins and a wide range of drugs nigam et al. A canalicular multispecific organic anion transporter 1 that is encoded in the genome of human.
In 1997, the multispecific organic anion transporter, organic anion transporter 1 oat1, 1 was first isolated from rat kidney cdna library by the expression cloning method 6,7. Organic anion transporter 1 how is organic anion transporter 1 abbreviated. Oat1 and 3 are predominantly renal anionexchanging antiporters responsible for the uptake of substrates from the blood into renal proximal tubular cells. Immunotag canalicular multispecific organic anion transporter 2 elisa kit. Genomic structure of the canalicular multispecific organic aniontransporter gene mrp2cmoat and mutations in the atpbindingcassette region in dubinjohnson syndrome. Implications for renal drug toxicity ling zou, adrian stecula, anshul gupta, bhagwat prasad, huanchieh chien, sook wah yee. It is a member of the organic anion transporter oat family of proteins. Abc news live coverage abc news 9,115 watching live now.
Flicek p, bork p, suyama m, bailey ja, portnoy me, torrents d, chinwalla at, gish. Anti human organic anion transporter 2 oat2 polyclonal. Organic anion transporter f definition of organic anion. Expression of organic anion transporter 1 or 3 in human. May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Phylogentically, organic anion transporter oat 1 and oat3 are closely related, whereas oat2 is more distant. Shared ligands between organic anion transporters oat1. Also transports sulfated bile salt such as taurolithocholate sulfate pubmed. Identification and characterization of human organic anion. Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
During the last decade, molecular cloning has identified several families of multispecific organic anion transporters mediating the renal and hepatic elimination of organic anions and, most recently, the oat organic anion transporter. Receive exclusive offers and updates from oxford academic. Organic anion transporters oats transporters iuphar. Inhibition of organic anion transporters oats or the organic cation transporter oct 2 at the basolateral membrane of renal proximal tubule cells figure 3 decreases the cellular uptake of. Oct1 is a polyspecific, bidirectional, facilitative diffusional transporter with 12 predicted membrane spanning domains, and is predominantly expressed on the blood side basolateral membrane of hepatocytes. Oct, octncarnitine transport family, and oat are multispecific organic anion transpoters, the substrates of which include a lot of both endogeneous and exogeneous anions. One is the abc superfamily, which includes pglycoprotein, a multidrug resistance associated protein 11, 12 and a canalicular multispecific organic anion transporter cmoat. Apr 01, 1998 the canalicular apical membrane of the hepatocyte contains an atpdependent transport system for organic anions, known as the multispecific organic anion transporter cmoat. The canalicular apical membrane of the hepatocyte contains an atpdependent transport system for organic anions, known as the multispecific organic anion transporter cmoat. A human canalicular multispecific organic anion transporter cmoat gene is. Meaning of canicular multispecific organic anion transporter medical term. The deduced amino acid sequence of cmoat is 49% identical to that of the human.
It belongs to the mrp multidrug resistance protein subfamily of the atpbinding cassette abc transporter family 1. Multidrug resistanceassociated protein 2 wikipedia. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of. Multidrug resistanceassociated protein 2 mrp2 also called canalicular multispecific organic anion transporter 1 cmoat or atpbinding cassette sub family. Organic anion transporters oats are nonselective transporters prominent in the kidney, placenta and bloodbrain barrier. To date, at least two multispecific transporter families were identified. Induction of the multispecific organic anion transporter cmoatmrp2. The renal oats contribute to the excretion of many drugs and their metabolites that are important in clinical medicine. Canalicular multispecific organic anion transporter 2.
Characterization of a human renal organic anion transporter. Human oat1 was found to be expressed predominantly in the kidney and only weakly in the brain. Organic anion transporter 3 contributes to the regulation of. Common to oat1, oat2, and oat3 is their ability to transport cgmp. Canalicular multispecific organic anion transporter 1 drugbank. Yee sw, giacomini mm, shen h, humphreys wg, horng h, brian w, lai y, kroetz dl, giacomini km.
The hoat3 cdna consisted of 2179 base pairs that encoded a 543aminoacid residue protein with 12 putative transmembrane domains. The canalicular multispecific organic anion transporter cmoat, a member of the atpbinding cassette transporter family, mediates the transport of a broad range of nonbile salt organic anions. Loc111244969 multidrug resistanceassociated protein 1. Transporters oat1 organic anion transporter 1 slc22a6 c show summary. Various atpdependent transporters have been identified, such as a multispecific organic anion transporter canalicular multispecific organic ion transporter, cmoat, a bile acid transporter and several pglycoproteins. When expressed in xenopus laevis oocytes, nlt mediated uptake of organic anions, such as salicylate, acetylsalicylate, pge 2, dicarboxylates and p. Organic cation transporter 1 how is organic cation. Since human organic anion transporter 4 oat4slc22a11 is expressed in the kidney and mediates urate transport, we investigated the effects of a common variant of oat4slc22a11 on the susceptibility to gout. Abcc2 canalicular multispecific organic anion transporter 1. Genomic structure of the canalicular multispecific organic. Human organic anion transporter 2 is distinct from organic.
The deduced amino acid sequence of hoat3 showed 36 to 51% identity to those of other members of the oat family. Kidney, organic anion, multispecific organic anion transporter, tubular secretion, xenobiotics, renal localization, caveolin 2 introduction the kidney, as well as the liver, plays a primary role. Canalicular multispecific organic anion transporter 1. Transport across the canalicular membrane represents a major concentrative step. Organic anion transporter 4 organic anion transporters oats. Identification of multispecific organic anion transporter. Abcc3 canalicular multispecific organic anion transporter 2.
Slco4c1 belongs to the organic anion transporter oatp family. Organic anion transporter 2 transcript variant 1 shows broad. Organic anion transporter 2 transcript variant 1 shows. Search thousands of articles and collaborate with scientists around the globe. Organic anion transporter polypeptiderelated protein 1. The canalicular multispecific organic anion transporter. This fragment is located in regionsbelievedtobeimportant forligandsubstratepreference.
Assignment of the canalicular multispecific organic anion. Mediates hepatobiliary excretion of numerous organic anions and conjugated organic anions such as methotrexate, 17betaestradiol 17glucosiduronic acid. Multidrug resistanceassociated protein 2 mrp2 also called canalicular multispecific organic anion transporter 1 cmoat or atpbinding cassette subfamily. Toh s, wada m, uchiumi t, inokuchi a, makino y, horie y, adachi y, sakisaka s, kuwano m. Molecular mechanisms for species differences in organic. Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. Anti human organic anion transporter 2 oat2 polyclonal antibody. Oat1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles, and the basolateral membrane of proximal tubular cells of the. Organic anion transporter 1 oat1,9,10 a gene originally identified as novel kidney transporter nkt and proposed to function in organic ion received february, 2008. Shared ligands between organic anion transporters oat1 and. Oat1 and oat3 organic anion transporters 1 and 3 aliases. Pelis department of pharmacology, dalhousie university, halifax, ns, canada organic anion transporter 2 oat2 is likely important for renal and hepatic drug elimination.
Organic anion transporters oats play an essential role in the elimination of numerous endogenous and exogenous organic anions from the body. Also transports sulfated bile salt such as taurolithocholate sulfate. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. A common variant of organic anion transporter 4 oat4.
Canalicular multispecific organic anion transporter. Molecular mechanisms for species differences in organic anion. In the studies mentioned above, the sodiumphosphate cotransporter npt4 slc17a3, present in the apical membrane of proximal tubule epithelial cells was also found associated with uric acid levels and gout. Various atpdependent transporters have been identified, such as a multispecific organic anion transporter canalicular multispecific organic ion transporter, cmoat. Which of the following is not a major constituent of bile. Yurong lai, in transporters in drug discovery and development, 20. Human organic anion transporter 1oat1 encodes a 563 amino acid residue protein, and which is predicted 12 putative membranespanning protein. Can targeting organic anion transporter polypeptide oatp. Anti human organic anion transporter 1 oat1 polyclonal. Assignment of the canalicular multispecific organic anion transporter cmoat gene to human chromosome 10q24 and mouse chromosome 19d2 by fluorescent in situ hybridization.
Organic anion transporter 1 an overview sciencedirect. Involvement of multispecific organic anion transporter. Several families of multispecific organic anion and cation transporters, including oat family transporters, have recently. This multispecific organic anion transporter is the human homolog of the pig otav1 found to be involved in urate efflux. The organic anion transporter 1 oat1 also known as solute carrier family 22 member 6 slc22a6 is a protein that in humans is encoded by the slc22a6 gene. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets. Organic anion transporter 2 transcript variant 1 shows broad ligand selectivity when expressed in multiple cell lines adam g. Oat1 and 3 are predominantly renal anion exchanging antiporters responsible for the uptake of substrates from the blood into renal proximal tubular cells. Oatps are involved in the membrane transport of bile acids, conjugated steroids, thyroid hormone, eicosanoids, peptides, and numerous drugs in many tissues mikkaichi et al. Although bidirectional, it typically behaves as an uptake transporter in vivo, extracting substrates from the blood into the hepatocyte.
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