TY - JOUR
T1 - Cloning of the human thiamine transporter, a member of the folate transporter family
AU - Dutta, Binita
AU - Huang, Wei
AU - Molero, Mariela
AU - Kekuda, Ramesh
AU - Leibach, Frederick H.
AU - Devoe, Lawrence D
AU - Ganapathy, Vadivel
AU - Prasad, Puttur D
PY - 1999/11/5
Y1 - 1999/11/5
N2 - We have isolated a cDNA from human placenta, which, when expressed heterologously in mammalian cells, mediates the transport of the water- soluble vitamin thiamine. The cDNA codes for a protein of 497 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is widely expressed in human tissues. When expressed in HeLa cells, the cDNA induces the transport of thiamine (K(t) = 2.5 ± 0.6 μM) in a Na+-independent manner. The cDNA-mediated transport of thiamine is stimulated by an outwardly directed H+ gradient. Substrate specificity assays indicate that the transporter is specific to thiamine. Even though thiamine is an organic cation, the cDNA-induced thiamine transport is not inhibited by other organic cations. Similarly, thiamine is not a substrate for the known members of mammalian organic cation transporter family. The thiamine transporter gene, located on human chromosome 1q24, consists of 6 exons and is most likely the gene defective in the metabolic disorder, thiamine-responsive megaloblastic anemia. At the level of amino acid sequence, the thiamine transporter is most closely related to the reduced-folate transporter and thus represents the second member of the folate transporter family.
AB - We have isolated a cDNA from human placenta, which, when expressed heterologously in mammalian cells, mediates the transport of the water- soluble vitamin thiamine. The cDNA codes for a protein of 497 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is widely expressed in human tissues. When expressed in HeLa cells, the cDNA induces the transport of thiamine (K(t) = 2.5 ± 0.6 μM) in a Na+-independent manner. The cDNA-mediated transport of thiamine is stimulated by an outwardly directed H+ gradient. Substrate specificity assays indicate that the transporter is specific to thiamine. Even though thiamine is an organic cation, the cDNA-induced thiamine transport is not inhibited by other organic cations. Similarly, thiamine is not a substrate for the known members of mammalian organic cation transporter family. The thiamine transporter gene, located on human chromosome 1q24, consists of 6 exons and is most likely the gene defective in the metabolic disorder, thiamine-responsive megaloblastic anemia. At the level of amino acid sequence, the thiamine transporter is most closely related to the reduced-folate transporter and thus represents the second member of the folate transporter family.
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U2 - 10.1074/jbc.274.45.31925
DO - 10.1074/jbc.274.45.31925
M3 - Article
C2 - 10542220
AN - SCOPUS:0033527646
SN - 0021-9258
VL - 274
SP - 31925
EP - 31929
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -