SLC19A2/3 transport extracellular THMN to cytosol

Stable Identifier
Reaction [transition]
Homo sapiens
Thiamin transport across the plasma membrane, thiamin [extracellular] => thiamin [cytosol]
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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.

Literature References
PubMed ID Title Journal Year
16705148 Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms

Said, HM, Ashokkumar, B, Vaziri, ND

Am J Physiol Renal Physiol 2006
14615284 Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine

Said, HM, Subramanian, VS, Marchant, JS, Balamurugan, K

Am J Physiol Gastrointest Liver Physiol 2004
16790503 Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2

Said, HM, Subramanian, VS, Marchant, JS

Am J Physiol Cell Physiol 2006
10391222 The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter

Cohen, N, Tartaglini, E, Fleming, JC, Schorderet, DF, Steinkamp, MP, Neufeld, EJ

Nat Genet 1999
10391223 Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome

Banikazemi, M, Oishi, K, Gelb, BD, Diaz, GA, Desnick, RJ

Nat Genet 1999
16371350 Targeting and trafficking of the human thiamine transporter-2 in epithelial cells

Said, HM, Subramanian, VS, Marchant, JS

J Biol Chem 2006
10391221 Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness

Cohen, N, Nosaka, K, Williams, H, Mandel, H, Gregory, S, McDonald, L, Baron, D, Labay, V, Szargel, R, Barrett, T, Shalata, A, Raz, T

Nat Genet 1999
Catalyst Activity

thiamine transmembrane transporter activity of SLC19A2/3 [plasma membrane]

Orthologous Events
Cross References
Cite Us!