SLC19A3 encodes a second thiamine transporter ThTr2

Abstract

Recently, a new family of facilitative carriers has been cloned consisting of the reduced folate (SLC19A1) and the thiamine (SLC19A2) transporters. Despite a high level of sequence identity and similarity there is essentially no functional overlap between these carriers. The former transports folates and the latter thiamine. 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. Uptake of [3H]thiamine, but not of methotrexate nor folic acid, was enhanced in SLC19A3 transfectants relative to vector control. Similarly, in the transfectants thiamine transport increased with an increase in pH with peak activity at pH approximately 7.5. While [3H]thiamine uptake was markedly inhibited by nonlabeled thiamine it was not inhibited by several organic cations in 100-fold excess. Hence this carrier has a high degree of specificity for vitamin B1. The data indicate that SLC19A3 has the characteristics of SLC19A2 (ThTr1) and represents a second thiamine transporter (ThTr2) in this family of facilitative carriers.

Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2

“…Evidence that hTHTR2 is a functional thiamine transporter derives from both overexpression (6,30,37), as well as silencing approaches (34). Indeed, hTHTR2 shows high structural identity to hTHTR1 (ϳ48%), a known thiamine transporter, compared with only ϳ17% to hSMVT, a known biotin transporter.…”

“…One such condition, thiamine-responsive megaloblastic anemia (9,12,22,26), was shown to be an inherited disorder rather than a result of dietary deficiency, which catalyzed the identification of the first human thiamine transporter (hTHTR1, as the product of the SLC19A2 gene). A second hTHTR (hTHTR2; as the product of the SLC19A3 gene) was subsequently identified via homology cloning [ϳ48% identity at the amino acid level (11,30)], and these two transporters have consequently been shown by several different laboratories to be saturable, high-affinity thiamine transporters with often overlapping tissue distribution but divergent targeting in polarized cells (6,30,34,37). Both thiamine transporters belong to the major facilitator superfamily of transport proteins, which have a predicted topology of 12 transmembrane (TM) domains between cytoplasmic NH 2 -and COOH-termini, together with a large cytoplasmic loop between TM6 and TM7, connecting the pseudosymmetrical TM1-6 and TM7-12 domains (10,11).…”

Characterization of a Folate Transporter in HeLa Cells with a Low pH Optimum and High Affinity for Pemetrexed Distinct from the Reduced Folate Carrier

“…The many similar features between the low pH transporter in R5 cells and transport mediated by RFC suggest that these carriers may share structural as well as functional similarities and raise the possibility that the low pH route may represent another member of the SLC19 family of membrane carriers. However, beyond RFC (SLC19A1), the other two members of this family (SLC19A2 and SLC19A3) are thiamine carriers that do not transport folates (35,36), and a genomewide search does not suggest that there are other members of this transport family.…”

Different Involvement of DNA Methylation and Histone Deacetylation in the Expression of Solute-Carrier Transporters in 4 Colon Cancer Cell Lines

“…Another transporter with high homology to these carriers has been identified, SLC19A3 (THTR2). 35) THTR2 represents second thiamine transporter. Patients with advanced cancer are known to often show thiamine deficiency.…”