Slc22a1

Summary

Gene Symbol: Slc22a1
Description: solute carrier family 22 (organic cation transporter), member 1
Alias: Lx1, Oct1, Orct, Orct1, solute carrier family 22 member 1, mOCT1, organic cation transporter 1, solute carrier family 22, member 1
Species: mouse
Products:     Slc22a1

Top Publications

  1. Mesplede T, Island M, Christeff N, Petek F, Doly J, Navarro S. The POU transcription factor Oct-1 represses virus-induced interferon A gene expression. Mol Cell Biol. 2005;25:8717-31 pubmed
    ..Finally, the IFN-A expression pattern is modified in Oct-1-deficient MEFs. The broad representation of effective and potent octamer-like sequences within IFN-A promoters suggests an important role for Oct-1 in IFN-A regulation. ..
  2. Jonker J, Wagenaar E, Van Eijl S, Schinkel A. Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations. Mol Cell Biol. 2003;23:7902-8 pubmed
    The polyspecific organic cation transporters 1 and 2 (Oct1 and -2) transport a broad range of substrates, including drugs, toxins, and endogenous compounds...
  3. Verhaagh S, Schweifer N, Barlow D, Zwart R. Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3) identifies a conserved cluster of three organic cation transporters on mouse chromosome 17 and human 6q26-q27. Genomics. 1999;55:209-18 pubmed
    ..between the Igf2r and Plg genes in close association with two additional members of the Slc22a gene family, mouse Slc22a1 and Slc22a2. A partial cDNA sequence of the human SLC22A3 gene was reconstituted from sequenced EST clones...
  4. Mooslehner K, Allen N. Cloning of the mouse organic cation transporter 2 gene, Slc22a2, from an enhancer-trap transgene integration locus. Mamm Genome. 1999;10:218-24 pubmed
    ..transporter with 12 putative transmembrane domains, that shares significant homology with the mouse organic cation transporter 1 (Oct1/Slc22a1) called Lx1...
  5. Zabel M, Wheeler W, Weis J, Weis J. Yin Yang 1, Oct1, and NFAT-4 form repeating, cyclosporin-sensitive regulatory modules within the murine CD21 intronic control region. J Immunol. 2002;168:3341-50 pubmed
    ..supershift analyses reveal the formation of multiple DNA-protein complexes at these sites that include Yin Yang 1, Oct1, and NFAT-4...
  6. Jonker J, Wagenaar E, Mol C, Buitelaar M, Koepsell H, Smit J, et al. Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene. Mol Cell Biol. 2001;21:5471-7 pubmed
    The polyspecific organic cation transporter 1 (OCT1 [SLC22A1]) mediates facilitated transport of small (hydrophilic) organic cations...
  7. Liu L, Du Z, Zhao H, Liu X, Huang X, Shen J, et al. T to C substitution at -175 or -173 of the gamma-globin promoter affects GATA-1 and Oct-1 binding in vitro differently but can independently reproduce the hereditary persistence of fetal hemoglobin phenotype in transgenic mice. J Biol Chem. 2005;280:7452-9 pubmed
    ..Both the -173 and -175 T to C substitutions may disrupt the complex assembly and result in the reactivation of the gamma-globin gene in adult erythrocytes. ..
  8. Zhao F, Adachi K, Oka T. Involvement of Oct-1 in transcriptional regulation of beta-casein gene expression in mouse mammary gland. Biochim Biophys Acta. 2002;1577:27-37 pubmed
    ..The binding activity in vivo can be induced by injection of progesterone or its combination with estradiol in virgin mice. ..
  9. Shu Y, Brown C, Castro R, Shi R, Lin E, Owen R, et al. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther. 2008;83:273-80 pubmed
    The goal of this study was to determine the effects of genetic variation in the organic cation transporter 1, OCT1, on the pharmacokinetics of the antidiabetic drug, metformin...

More Information

Publications46

  1. Eisner C, Faulhaber Walter R, Wang Y, Leelahavanichkul A, Yuen P, Mizel D, et al. Major contribution of tubular secretion to creatinine clearance in mice. Kidney Int. 2010;77:519-26 pubmed publisher
    ..Creatinine secretion in both genders was not mediated by the organic cation transporters OCT1 or OCT 2 since secretion fraction levels were identical in FVB wild-type and OCT1/2 knockout mice...
  2. Pabla N, Gibson A, Buege M, Ong S, Li L, Hu S, et al. Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions. Proc Natl Acad Sci U S A. 2015;112:5231-6 pubmed publisher
    ..The unique cell-cycle and OCT2-targeting activities of palbociclib and LEE011, combined with their potential for clinical translation, support their further exploration as therapeutic candidates for prevention of AKI. ..
  3. More S, Li S, Yee S, Chen L, Xu Z, Jablons D, et al. Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third-generation platinum analogue. Mol Cancer Ther. 2010;9:1058-69 pubmed publisher
    ..This effort was aimed at the determination of the influence of organic cation transporters 1, 2, and 3 (OCT1, OCT2, and OCT3) and their genetic variants on cellular uptake of picoplatin and on the individual components of ..
  4. Koehler M, Wissinger B, Gorboulev V, Koepsell H, Schmid M. The two human organic cation transporter genes SLC22A1 and SLC22A2 are located on chromosome 6q26. Cytogenet Cell Genet. 1997;79:198-200 pubmed
    ..We have localized the OCT1 and OCT2 genes (SLC22A1, SLC22A2) on chromosome 6q26.
  5. Kam K, Jeong K, Norwitz E, Jorgensen E, Kaiser U. Oct-1 and nuclear factor Y bind to the SURG-1 element to direct basal and gonadotropin-releasing hormone (GnRH)-stimulated mouse GnRH receptor gene transcription. Mol Endocrinol. 2005;19:148-62 pubmed
    ..In conclusion, NF-Y and Oct-1 bind to the SURG-1 element to direct basal and GnRH-stimulated expression of the mGnRHR gene. ..
  6. Yang J, Kalogerou M, Gallacher J, Sampson J, Shen M. Renal tumours in a Tsc1+/- mouse model show epigenetic suppression of organic cation transporters Slc22a1, Slc22a2 and Slc22a3, and do not respond to metformin. Eur J Cancer. 2013;49:1479-90 pubmed publisher
    ..Surprisingly, the expression of the organic cation transporters Slc22a1, Slc22a2 and Slc22a3 essential for the cellular uptake of metformin was highly suppressed in renal tumours...
  7. Lips K, Luhrmann A, Tschernig T, Stoeger T, Alessandrini F, Grau V, et al. Down-regulation of the non-neuronal acetylcholine synthesis and release machinery in acute allergic airway inflammation of rat and mouse. Life Sci. 2007;80:2263-9 pubmed
    ..acetyltransferase (ChAT), the vesicular ACh transporter (VAChT), and the polyspecific organic cation transporters (OCT1-3), which are able to translocate choline and ACh across the plasma membrane...
  8. Pauler F, Stricker S, Warczok K, Barlow D. Long-range DNase I hypersensitivity mapping reveals the imprinted Igf2r and Air promoters share cis-regulatory elements. Genome Res. 2005;15:1379-87 pubmed
    ..These results refine our understanding of the onset of imprinted silencing at this cluster and indicate the Air noncoding RNA may specifically target silencing to the Igf2r promoter. ..
  9. Yosef N, Shalek A, Gaublomme J, Jin H, Lee Y, Awasthi A, et al. Dynamic regulatory network controlling TH17 cell differentiation. Nature. 2013;496:461-8 pubmed publisher
    ..Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling TH17 cell differentiation. ..
  10. Chen L, Shu Y, Liang X, Chen E, Yee S, Zur A, et al. OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. Proc Natl Acad Sci U S A. 2014;111:9983-8 pubmed publisher
    b>Organic cation transporter 1, OCT1 (SLC22A1), is the major hepatic uptake transporter for metformin, the most prescribed antidiabetic drug. However, its endogenous role is poorly understood...
  11. Lammert F, Wang D, Wittenburg H, Bouchard G, Hillebrandt S, Taenzler B, et al. Lith genes control mucin accumulation, cholesterol crystallization, and gallstone formation in A/J and AKR/J inbred mice. Hepatology. 2002;36:1145-54 pubmed
    ..Characterization of the pathophysiologic roles of Lith3 and the new biliary mucin gene Glycam1 might provide insights into primary defects of human cholelithiasis and lead to new therapeutic strategies for prestone intervention. ..
  12. Liu M, Leibowitz J, Clark D, Mendicino M, Ning Q, Ding J, et al. Gene transcription of fgl2 in endothelial cells is controlled by Ets-1 and Oct-1 and requires the presence of both Sp1 and Sp3. Eur J Biochem. 2003;270:2274-86 pubmed
  13. Cui J, Gunewardena S, Yoo B, Liu J, Renaud H, Lu H, et al. RNA-Seq reveals different mRNA abundance of transporters and their alternative transcript isoforms during liver development. Toxicol Sci. 2012;127:592-608 pubmed publisher
    ..In adult liver, the transporters with highest expression were organic cation transporter 1 and Ntcp (23% and 22%, respectively)...
  14. Shu Y, Sheardown S, Brown C, Owen R, Zhang S, Castro R, et al. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest. 2007;117:1422-31 pubmed
    Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which ..
  15. Schweifer N, Valk P, Delwel R, Cox R, Francis F, Meier Ewert S, et al. Characterization of the C3 YAC contig from proximal mouse chromosome 17 and analysis of allelic expression of genes flanking the imprinted Igf2r gene. Genomics. 1997;43:285-97 pubmed
    ..We further show that the recently identified Lx1 gene lies immediately downstream and is also expressed from both parental alleles in adult tissues...
  16. Nie W, Sweetser S, Rinella M, Green R. Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome proliferator agonist receptor-alpha and -gamma. Am J Physiol Gastrointest Liver Physiol. 2005;288:G207-12 pubmed
    ..The transport and metabolism of organic cationic endobiotics, nutrients, and drugs are essential hepatic functions. Slc22A1 is the basolateral liver transporter mediating the uptake of organic cations; however, little is known about the ..
  17. Kakehi M, Koyabu N, Nakamura T, Uchiumi T, Kuwano M, Ohtani H, et al. Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. Biochem Biophys Res Commun. 2002;296:644-50 pubmed
    ..1.1). Uptake of [(3)H]1-methyl-4-phenylpyridinium ([(3)H]MPP(+)) by Xenopus laevis oocytes injected with mOCT1 (Slc22a1) or mOCT2 (Slc22a2) cRNA was attenuated by an increase of extracellular K(+) concentration and under acidic ..
  18. Catena R, Tiveron C, Ronchi A, Porta S, Ferri A, Tatangelo L, et al. Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. J Biol Chem. 2004;279:41846-57 pubmed
    ..Oct4 might play a role in the regulation of Sox2 in ES (inner cell mass) cells and, possibly, at the transition between inner cell mass and neural cells, before recruitment of neural POU factors such as Brn1 and Brn2. ..
  19. Vallette Kasic S, Pellegrini Bouiller I, Sampieri F, Gunz G, Diaz A, Radovick S, et al. Combined pituitary hormone deficiency due to the F135C human Pit-1 (pituitary-specific factor 1) gene mutation: functional and structural correlates. Mol Endocrinol. 2001;15:411-20 pubmed
  20. Khomenko T, Kolodney J, Pinto J, McLaren G, Deng X, Chen L, et al. New mechanistic explanation for the localization of ulcers in the rat duodenum: role of iron and selective uptake of cysteamine. Arch Biochem Biophys. 2012;525:60-70 pubmed publisher
    ..b>OCT1 mRNA was markedly expressed in the rat duodenum and in IEC-6, and transfection of IEC-6 with OCT1 siRNA decreased ..
  21. Hollenhorst M, Lips K, Wolff M, Wess J, Gerbig S, Takats Z, et al. Luminal cholinergic signalling in airway lining fluid: a novel mechanism for activating chloride secretion via Ca²?-dependent Cl? and K? channels. Br J Pharmacol. 2012;166:1388-402 pubmed publisher
    ..Thus, this study focused on the effect of luminal ACh as a regulator of transepithelial ion transport in epithelial cells...
  22. Dong B, Huang C, Li D, Zhao F. Oct-1 functions as a transactivator in the hormonal induction of beta-casein gene expression. Mol Cell Biochem. 2009;328:93-9 pubmed publisher
  23. Dong B, Zhao F. Involvement of the ubiquitous Oct-1 transcription factor in hormonal induction of beta-casein gene expression. Biochem J. 2007;401:57-64 pubmed
    ..The results of the present study provide biochemical evidence that the ubiquitous Oct-1 transcription factor may be involved in hormonally regulated, tissue-specific beta-casein gene expression. ..
  24. Mashimo T, Erven A, Spiden S, Guenet J, Steel K. Two quantitative trait loci affecting progressive hearing loss in 101/H mice. Mamm Genome. 2006;17:841-50 pubmed
    ..Finally, we found some evidence of epistatic interaction between Phl1 and Phl2. ..
  25. Kummer W, Wiegand S, Akinci S, Wessler I, Schinkel A, Wess J, et al. Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse. Respir Res. 2006;7:65 pubmed
    ..Epithelial ACh content was significantly higher in OCT1/2 double-knockout mice (42 +/- 10 % of the content of the epithelium-denuded trachea, n = 9) than in wild-type mice ..
  26. Schweifer N, Barlow D. The Lx1 gene maps to mouse chromosome 17 and codes for a protein that is homologous to glucose and polyspecific transmembrane transporters. Mamm Genome. 1996;7:735-40 pubmed
    ..Lx1 most likely represents the mouse homolog of the rat gene OCT1, which encodes a polyspecific transmembrane transporter that is possibly involved in drug elimination...
  27. Green R, Lo K, Sterritt C, Beier D. Cloning and functional expression of a mouse liver organic cation transporter. Hepatology. 1999;29:1556-62 pubmed
    ..We have isolated a complementary DNA (cDNA) from both murine liver and kidney cDNA libraries (mOct1/Slc22a1), and have functionally expressed it in Xenopus laevis oocytes...
  28. Ciarimboli G, Deuster D, Knief A, Sperling M, Holtkamp M, Edemir B, et al. Organic cation transporter 2 mediates cisplatin-induced oto- and nephrotoxicity and is a target for protective interventions. Am J Pathol. 2010;176:1169-80 pubmed publisher
    ..excretion of glucose, water, and protein) and hearing (auditory brainstem response) were studied in wild-type and OCT1/2 double-knockout (KO) mice...
  29. Sebastiano V, Dalvai M, Gentile L, Schubart K, Sutter J, Wu G, et al. Oct1 regulates trophoblast development during early mouse embryogenesis. Development. 2010;137:3551-60 pubmed publisher
    b>Oct1 (Pou2f1) is a transcription factor of the POU-homeodomain family that is unique in being ubiquitously expressed in both embryonic and adult mouse tissues...
  30. Monte J, Nagle M, Eraly S, Nigam S. Identification of a novel murine organic anion transporter family member, OAT6, expressed in olfactory mucosa. Biochem Biophys Res Commun. 2004;323:429-36 pubmed
    ..Supporting this possibility, we have demonstrated that OAT1, OCT1-2, and OCTN1-3 are also expressed in olfactory mucosa...
  31. Schlatter E, Klassen P, Massmann V, Holle S, Guckel D, Edemir B, et al. Mouse organic cation transporter 1 determines properties and regulation of basolateral organic cation transport in renal proximal tubules. Pflugers Arch. 2014;466:1581-9 pubmed
    The proximal tubule of mouse kidney expresses mouse organic cation transporter 1 (mOCT1), mOCT2, and much less mOCT3...
  32. Pavlova A, Sakurai H, Leclercq B, Beier D, Yu A, Nigam S. Developmentally regulated expression of organic ion transporters NKT (OAT1), OCT1, NLT (OAT2), and Roct. Am J Physiol Renal Physiol. 2000;278:F635-43 pubmed
    ..examined the spatiotemporal expression patterns of representative organic ion transporters, [NKT (OAT1), Roct, OCT1, and NLT, also known as OAT2] during murine development...
  33. Sprowl J, Ong S, Gibson A, Hu S, Du G, Lin W, et al. A phosphotyrosine switch regulates organic cation transporters. Nat Commun. 2016;7:10880 pubmed publisher
  34. Zwart R, Sleutels F, Wutz A, Schinkel A, Barlow D. Bidirectional action of the Igf2r imprint control element on upstream and downstream imprinted genes. Genes Dev. 2001;15:2361-6 pubmed
    ..These results identify a new cluster of imprinted genes whose repression by the bidirectional action of the Region2-ICE is independent of transcript overlap by the Air RNA. ..
  35. Zwart R, Verhaagh S, De Jong J, Lyon M, Barlow D. Genetic analysis of the organic cation transporter genes Orct2/Slc22a2 and Orct3/Slc22a3 reduces the critical region for the t haplotype mutant t(w73) to 200 kb. Mamm Genome. 2001;12:734-40 pubmed
    ..The results eliminate both Orct2 and Orct3 as candidates and further reduce the critical region containing the t(w73) mutant from 500 kb to 200 kb. ..
  36. Chen R, Jonker J, Nelson J. Renal organic cation and nucleoside transport. Biochem Pharmacol. 2002;64:185-90 pubmed
    ..To evaluate the potential of OCT1 in the renal secretion of dTub, tissue distribution and urinary excretion of dTub in OCT1 knockout mice were ..
  37. Wang D, Jonker J, Kato Y, Kusuhara H, Schinkel A, Sugiyama Y. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002;302:510-5 pubmed
    ..The purpose of the present study was to investigate the role of organic cation transporter 1 (Oct1) in the disposition of metformin...