High impact information on SLC19A3

• Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3 [1].
• Targeting and trafficking of the human thiamine transporter-2 in epithelial cells [2].
• Deletion analysis identified the differentiation-responsive region to be at position -356 to -275 bp for the SLC19A2 promoter and at position -77 to -13 bp for the SLC19A3 promoter [3].
• These data provide evidence that expression of SLC19A3 is a relatively sensitive indicator of marginal biotin deficiency [4].
• Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood [4].

Biological context of SLC19A3

• The human SLC19A3 gene is widely expressed, with the most abundant expression observed in placenta, kidney, and liver, and has been mapped to chromosome 2q37 [5].
• In this paper we describe the function of SLC19A3, another member of this transporter family most recently cloned, after transient transfection of the cDNA into HeLa cells [6].
• These studies demonstrate for the first time that differentiation of intestinal epithelial cells is associated with an up-regulation in thiamin uptake process and that this up-regulation appears to be mediated via transcriptional regulatory mechanisms that involve the SLC19A2 and SLC19A3 genes [3].
• With the use of transiently transfected human intestinal epithelial Caco-2 cells and 5'-deletion analysis, the minimal promoter region required for basal activity of the SLC19A3 promoter was found to be encoded in a sequence between -77 and +59 by using the start of transcription initiation as position 1 [7].
• Functionality of the full-length SLC19A3 promoter was confirmed in vivo in transgenic mice expressing the promoter-luciferase reporter gene [7].

Associations of SLC19A3 with chemical compounds

• Identification and characterization of the human and mouse SLC19A3 gene: a novel member of the reduced folate family of micronutrient transporter genes [5].
• Uptake of [3H]thiamine, but not of methotrexate nor folic acid, was enhanced in SLC19A3 transfectants relative to vector control [6].

Other interactions of SLC19A3

• SLC19A3 encodes a second thiamine transporter ThTr2 [6].
• These studies report the first characterization of the SLC19A3 promoter in vitro and in vivo and demonstrate the importance of an SP1 cis-regulatory element in regulating promoter activity of this important human gene [7].
• In transiently transfected Drosophila SL2 cells, both SP1 and SP3 transactivated the SLC19A3 minimal promoter in a dose-dependent manner and in combination demonstrated an additive stimulatory effect [7].

References