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Gene Review

Slc19a1  -  solute carrier family 19 (folate...

Rattus norvegicus

Synonyms: Folate transporter 1, RFC-1, RFC1, Reduced folate carrier 1, Solute carrier family 19 member 1
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Disease relevance of Slc19a1


Psychiatry related information on Slc19a1


High impact information on Slc19a1

  • The basis of this strategy is that methotrexate-alpha-peptides are inefficient substrates for the reduced folate carrier (RFC) and hence cannot be internalized by cells [4].
  • Uptake of [3H]MTX and [3H]folinic acid, but not [3H]folic acid, by H35 cells was inhibited in a dose-related manner by PT523, suggesting that penetration of the cell probably involves, at least in part, active transport by the MTX/reduced folate carrier [5].
  • However, influx of [(3)H]MTX by this system is 3-4-fold higher at pH 6 than at pH 7.5, the optimum for RFC-1-mediated folate compound transport [6].
  • The relative inhibition of influx of [(3)H]MTX by the organic anions, probenecid, and PO(4) was different than for RFC-1 mediated influx [6].
  • This downregulation of the acid pH dependent system and concomitant upregulation of the RFC-1 mediated system markedly altered pH dependency for influx of [(3)H]MTX in these transfectants compared to that seen in untransfected cells [6].

Biological context of Slc19a1

  • This was contrasted with the results of transfection of the same RFC1 construct into an L1210 murine leukemia cell line bearing a nonfunctional endogenous carrier [7].
  • Recently, the rat genome project revealed the genomic sequence of slc19a1, coding for the methotrexate carrier-1, identical to the reduced folate carrier-1 of humans, on rat chromosome 20 [8].
  • We conclude that the major route for internalization at a physiological pH of folate compounds in FR3T3 cells is by an acid pH-dependent carrier-mediated system independent of RFC-1 expression and is downregulated by oncogene expression [6].
  • The increase in RFC-1 expression in FR3T3Hras cells appears to result from a higher rate of transcription of the gene in these cells as determined by a luciferase reporter gene assay of RFC-1 promoter activity [6].
  • RT-PCR analysis indicated gene expression of Oat2, Oatplal, Oatpla4, Oatplb2, Rfc-1/MTX-1, FOLR, Mrp1-6, mdr1, and Lrp [9].

Anatomical context of Slc19a1


Associations of Slc19a1 with chemical compounds

  • Here, we report on the cloning of the cDNA for the renal methotrexate carrier isoform-1 (RK-MTX-1) and its functional characterization [1].
  • 4. These data indicate that RFC1 can exhibit two distinct types of folate transport activities in intestinal cells that must depend on tissue-specific modulators [7].
  • 4. Transfection of this cell line with an RFC1 construct resulted in clones exhibiting increased MTX uptake at both the pHs and high folic acid uptake only at the low pH [7].
  • NSAIDs, except salicylate, were potent inhibitors of rOat3 (K(i) of 1.3-19 microM), but weak inhibitors of RFC-1 (K(i) of 70-310 microM) [13].
  • These results suggest that rOat3 and RFC-1 are almost equally involved in the uptake of MTX by the kidney slices, whereas RFC-1 is responsible for the renal uptake of 5-methyltetrahydrofolate [13].

Analytical, diagnostic and therapeutic context of Slc19a1

  • Western blot analysis of BBM protein and real-time PCR showed RFC protein and mRNA levels, respectively, to be significantly (P < 0.01 for both) higher in suckling compared with weanling rats, which were in turn significantly (P < 0.01 for both) higher than that in adult rats [11].
  • Quantitative evaluation of the drug-drug interactions between methotrexate and nonsteroidal anti-inflammatory drugs in the renal uptake process based on the contribution of organic anion transporters and reduced folate carrier [13].


  1. Sodium-dependent methotrexate carrier-1 is expressed in rat kidney: cloning and functional characterization. Kneuer, C., Honscha, K.U., Honscha, W. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  2. Effects of non-steroidal anti-inflammatory drugs on the methotrexate transport in rat small intestine. Sosogi, A., Gao, F., Tomimatsu, T., Hirata, K., Horie, T. Scand. J. Gastroenterol. (2003) [Pubmed]
  3. Expression of varying portions of the adenovirus 12 early region 1 in transformed cells affects tumorigenicity and interaction with extracellular matrix components. Bober, F.J., Birk, D.E., Raska, K. Lab. Invest. (1987) [Pubmed]
  4. Toward an enzyme/prodrug strategy for cancer gene therapy: endogenous activation of carboxypeptidase A mutants by the PACE/Furin family of propeptidases. Hamstra, D.A., Rehemtulla, A. Hum. Gene Ther. (1999) [Pubmed]
  5. Biochemical studies on PT523, a potent nonpolyglutamatable antifolate, in cultured cells. Rhee, M.S., Galivan, J., Wright, J.E., Rosowsky, A. Mol. Pharmacol. (1994) [Pubmed]
  6. Contrasting effects of oncogene expression on two carrier-mediated systems internalizing folate compounds in Fisher rat 3T3 cells. Kühnel, J.M., Chiao, J.H., Sirotnak, F.M. J. Cell. Physiol. (2000) [Pubmed]
  7. Expression of the reduced folate carrier SLC19A1 in IEC-6 cells results in two distinct transport activities. Rajgopal, A., Sierra, E.E., Zhao, R., Goldman, I.D. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  8. Alternative transcripts of rat slc19a1: cloning, genomic organisation, tissue specific promoters and alternative splicing. Kneuer, C., Schrader, S., Honscha, W. DNA Seq. (2005) [Pubmed]
  9. Endogenous expression of liver-specific drug transporters for organic anions in the rat hepatocytoma fusion cell line HPCT-1E3. Halwachs, S., Kneuer, C., Honscha, W. Eur. J. Cell Biol. (2005) [Pubmed]
  10. Preservation of folate transport activity with a low-pH optimum in rat IEC-6 intestinal epithelial cell lines that lack reduced folate carrier function. Wang, Y., Rajgopal, A., Goldman, I.D., Zhao, R. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  11. Ontogenic regulation of folate transport across rat jejunal brush-border membrane. Balamurugan, K., Said, H.M. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  12. Role of reduced folate carrier in intestinal folate uptake. Balamurugan, K., Said, H.M. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  13. Quantitative evaluation of the drug-drug interactions between methotrexate and nonsteroidal anti-inflammatory drugs in the renal uptake process based on the contribution of organic anion transporters and reduced folate carrier. Nozaki, Y., Kusuhara, H., Endou, H., Sugiyama, Y. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
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