SLC22A1 explained

Solute carrier family 22 member 1 is a protein that in humans is encoded by the gene SLC22A1.^{[1] [2]}

Function

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. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter.

It is also required for the uptake of metformin by cells.^{[3] [4]}

See also

• Solute carrier family
• Organic cation transport proteins

Further reading

• Berkhout B, Jeang KT . Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat . Journal of Virology . 66 . 1 . 139–49 . January 1992 . 1727476 . 238269 . 10.1128/JVI.66.1.139-149.1992.
• Jeang KT, Chun R, Lin NH, Gatignol A, Glabe CG, Fan H . In vitro and in vivo binding of human immunodeficiency virus type 1 Tat protein and Sp1 transcription factor . Journal of Virology . 67 . 10 . 6224–33 . October 1993 . 7690421 . 238044 . 10.1128/JVI.67.10.6224-6233.1993.
• Liu YZ, Lania L, Latchman DS . Functional interaction between the HIV-1 Tat transactivator and the inhibitory domain of the Oct-2 cellular transcription factor . AIDS . 10 . 12 . 1323–9 . October 1996 . 8902060 . 10.1097/00002030-199610000-00003 . 11659500 .
• Liu YZ, Latchman DS . The octamer-binding proteins Oct-1 and Oct-2 repress the HIV long terminal repeat promoter and its transactivation by Tat . The Biochemical Journal . 322 . Pt 1 . 155–8 . February 1997 . 9078256 . 1218171 . 10.1042/bj3220155.
• Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM . Cloning and functional expression of a human liver organic cation transporter . Molecular Pharmacology . 51 . 6 . 913–21 . June 1997 . 9187257 . 10.1124/mol.51.6.913. 30839969 .
• Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H . Cloning and characterization of two human polyspecific organic cation transporters . DNA and Cell Biology . 16 . 7 . 871–81 . July 1997 . 9260930 . 10.1089/dna.1997.16.871 .
• Verhaagh S, Schweifer N, Barlow DP, 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 . 55 . 2 . 209–18 . January 1999 . 9933568 . 10.1006/geno.1998.5639 .
• Chasman D, Cepek K, Sharp PA, Pabo CO . Crystal structure of an OCA-B peptide bound to an Oct-1 POU domain/octamer DNA complex: specific recognition of a protein-DNA interface . Genes & Development . 13 . 20 . 2650–7 . October 1999 . 10541551 . 317104 . 10.1101/gad.13.20.2650 .
• Tomilin A, Reményi A, Lins K, Bak H, Leidel S, Vriend G, Wilmanns M, Schöler HR . Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration . Cell . 103 . 6 . 853–64 . December 2000 . 11136971 . 10.1016/S0092-8674(00)00189-6 . 14650955 . free .
• Hayer M, Bönisch H, Brüss M . Molecular cloning, functional characterization and genomic organization of four alternatively spliced isoforms of the human organic cation transporter 1 (hOCT1/SLC22A1) . Annals of Human Genetics . 63 . Pt 6 . 473–82 . November 1999 . 11388889 . 10.1046/j.1469-1809.2000.6430267.x. 221419328 . free .
• Pietig G, Mehrens T, Hirsch JR, Cetinkaya I, Piechota H, Schlatter E . Properties and regulation of organic cation transport in freshly isolated human proximal tubules . The Journal of Biological Chemistry . 276 . 36 . 33741–6 . September 2001 . 11447227 . 10.1074/jbc.M104617200 . free .
• Pan H, Qin WX, Huo KK, Wan DF, Yu Y, Xu ZG, Hu QD, Gu KT, Zhou XM, Jiang HQ, Zhang PP, Huang Y, Li YY, Gu JR . Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1 . Genomics . 77 . 1–2 . 58–64 . September 2001 . 11543633 . 10.1006/geno.2001.6614 .
• Xu XR, Huang J, Xu ZG, Qian BZ, Zhu ZD, Yan Q, Cai T, Zhang X, Xiao HS, Qu J, Liu F, Huang QH, Cheng ZH, Li NG, Du JJ, Hu W, Shen KT, Lu G, Fu G, Zhong M, Xu SH, Gu WY, Huang W, Zhao XT, Hu GX, Gu JR, Chen Z, Han ZG . Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver . Proceedings of the National Academy of Sciences of the United States of America . 98 . 26 . 15089–94 . December 2001 . 11752456 . 64988 . 10.1073/pnas.241522398 . 2001PNAS...9815089X . free .
• Schinkel AH, Jonker JW . Polymorphisms affecting function of the human organic cation transporter hOCT1 (SLC22A1): what are the consequences? . Pharmacogenetics . 12 . 8 . 589–90 . November 2002 . 12439217 . 10.1097/00008571-200211000-00001 .
• Kerb R, Brinkmann U, Chatskaia N, Gorbunov D, Gorboulev V, Mornhinweg E, Keil A, Eichelbaum M, Koepsell H . Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences . Pharmacogenetics . 12 . 8 . 591–5 . November 2002 . 12439218 . 10.1097/00008571-200211000-00002 .
• Schaffer A, Kim EC, Wu X, Zan H, Testoni L, Salamon S, Cerutti A, Casali P . Selective inhibition of class switching to IgG and IgE by recruitment of the HoxC4 and Oct-1 homeodomain proteins and Ku70/Ku86 to newly identified ATTT cis-elements . The Journal of Biological Chemistry . 278 . 25 . 23141–50 . June 2003 . 12672812 . 10.1074/jbc.M212952200 . free .
• Shu Y, Leabman MK, Feng B, Mangravite LM, Huang CC, Stryke D, Kawamoto M, Johns SJ, DeYoung J, Carlson E, Ferrin TE, Herskowitz I, Giacomini KM . Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1 . Proceedings of the National Academy of Sciences of the United States of America . 100 . 10 . 5902–7 . May 2003 . 12719534 . 156299 . 10.1073/pnas.0730858100 . 2003PNAS..100.5902S . free .
• Sakata T, Anzai N, Shin HJ, Noshiro R, Hirata T, Yokoyama H, Kanai Y, Endou H . Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions . Biochemical and Biophysical Research Communications . 313 . 3 . 789–93 . January 2004 . 14697261 . 10.1016/j.bbrc.2003.11.175 .
• Bottalico B, Larsson I, Brodszki J, Hernandez-Andrade E, Casslén B, Marsál K, Hansson SR . Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies . Placenta . 25 . 6 . 518–29 . July 2004 . 15135235 . 10.1016/j.placenta.2003.10.017 .

Notes and References

1. Koehler MR, Wissinger B, Gorboulev V, Koepsell H, Schmid M . The two human organic cation transporter genes SLC22A1 and SLC22A2 are located on chromosome 6q26 . Cytogenetics and Cell Genetics . 79 . 3–4 . 198–200 . Jun 1998 . 9605850 . 10.1159/000134720 .
2. Web site: Entrez Gene: SLC22A1 solute carrier family 22 (organic cation transporter), member 1.
3. Pryor. R. Cabreiro. F. Haberland. G. Repurposing metformin: an old drug with new tricks in its binding pockets. Biochemical Journal. 16 October 2015. 471. 3. 307–322. 10.1042/BJ20150497. 26475449. 4613459.
4. Rosilio. C. Ben-Sahra. I. Bost. F. Peyron. JF. Metformin: a metabolic disruptor and anti-diabetic drug to target human leukemia.. Cancer Letters. 1 May 2014. 346. 2. 188–96. 10.1016/j.canlet.2014.01.006. 24462823.