Two transport proteins, SLC19A2 (THTR1) and SLC19A3 (THTR2), associated with the plasma membrane, are each able to mediate the transport of extracellular thiamin into the cytosol. In the body, both transporters are widely distributed, and both are abundant in kidney and intestinal epithelia, consistent with their involvement in thiamin uptake under physiological conditions (Ashokkumar et al. 2006; Said et al. 2004; Subramanian et al. 2006 - J Biol Chem). The observation that mutations in SLC19A2 (THTR1) cause a progressive disorder that can be partially reversed by treatment with high doses of thiamin likewise suggests a role for this protein in thiamin uptake under normal conditions (Diaz et al. 1999; Fleming et al. 1999; Labay et al. 1999).
Two features of this transport process remain incompletely understood, however. First, mutations in SLC19A3 cause a progressive disorder that is responsive to biotin treatment (Zhou et al. 2005), although studies of cultured cells indicate that the protein has no affinity for biotin (Subramanian et al. 2006 - Am J Physiol). Also, studies to date provide little information about the mechanism by which thiamin, once taken up by epithelial cells in the intestine and kidney, is released from these cells into the blood.
|Synonyms||Thiamin transport across the plasma membrane|
|SLC19A2/3||thiamine transmembrane transporter activity (0015234)|
|16705148||Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms||Am J Physiol Renal Physiol||2006|
|10391223||Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome||Nat Genet||1999|
|10391222||The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter||Nat Genet||1999|
|10391221||Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness||Nat Genet||1999|
|14615284||Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine||Am J Physiol Gastrointest Liver Physiol||2004|
|16371350||Targeting and trafficking of the human thiamine transporter-2 in epithelial cells||J Biol Chem||2006|
|16790503||Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2||Am J Physiol Cell Physiol||2006|