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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Based on the proptypical member of this family, PCFT, this family includes proton-driven transporters with 11 TM segments. SLC46A1 has been described to act as an intestinal proton-coupled high-affinity folic acid transporter , with lower affinity for heme. Folic acid accumulation is independent of Na+ or K+ ion concentrations, but driven by extracellular protons with an as yet undefined stoichiometry.
* Key recommended reading is highlighted with an asterisk
* Anderson CM, Thwaites DT. (2010) Hijacking solute carriers for proton-coupled drug transport. Physiology (Bethesda), 25 (6): 364-77. [PMID:21186281]
* Desmoulin SK, Hou Z, Gangjee A, Matherly LH. (2012) The human proton-coupled folate transporter: Biology and therapeutic applications to cancer. Cancer Biol. Ther., 13 (14): 1355-73. [PMID:22954694]
* Hou Z, Matherly LH. (2014) Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr, 73: 175-204. [PMID:24745983]
Krishnamurthy P, Xie T, Schuetz JD. (2007) The role of transporters in cellular heme and porphyrin homeostasis. Pharmacol. Ther., 114 (3): 345-58. [PMID:17368550]
Latunde-Dada GO, Simpson RJ, McKie AT. (2006) Recent advances in mammalian haem transport. Trends Biochem. Sci., 31 (3): 182-8. [PMID:16487711]
* Matherly LH, Wilson MR, Hou Z. (2014) The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer. Drug Metab. Dispos., 42 (4): 632-49. [PMID:24396145]
* Thwaites DT, Anderson CM. (2007) H+-coupled nutrient, micronutrient and drug transporters in the mammalian small intestine. Exp. Physiol., 92 (4): 603-19. [PMID:17468205]
* Wilson MR, Kugel S, Huang J, Wilson LJ, Wloszczynski PA, Ye J, Matherly LH, Hou Z. (2015) Structural determinants of human proton-coupled folate transporter oligomerization: role of GXXXG motifs and identification of oligomeric interfaces at transmembrane domains 3 and 6. Biochem. J., [Epub ahead of print]. [PMID:25877470]
Wolf G. (2007) Identification of proton-coupled high-affinity human intestinal folate transporter mutated in human hereditary familial folate malabsorption. Nutr. Rev., 65 (12 Pt 1): 554-7. [PMID:18236695]
Yuasa H, Inoue K, Hayashi Y. (2009) Molecular and functional characteristics of proton-coupled folate transporter. J Pharm Sci, 98 (5): 1608-16. [PMID:18823045]
* Zhao R, Diop-Bove N, Visentin M, Goldman ID. (2011) Mechanisms of membrane transport of folates into cells and across epithelia. Annu. Rev. Nutr., 31: 177-201. [PMID:21568705]
* Zhao R, Goldman ID. (2013) Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors. Mol. Aspects Med., 34 (2-3): 373-85. [PMID:23506878]
1. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H. (2007) Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J. Pharmacol. Exp. Ther., 322 (2): 469-76. [PMID:17475902]
2. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID. (2006) Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell, 127 (5): 917-28. [PMID:17129779]
3. Salojin KV, Cabrera RM, Sun W, Chang WC, Lin C, Duncan L, Platt KA, Read R, Vogel P, Liu Q et al.. (2011) A mouse model of hereditary folate malabsorption: deletion of the PCFT gene leads to systemic folate deficiency. Blood, 117 (18): 4895-904. [PMID:21346251]
Database page citation:
SLC46 family of folate transporters. Accessed on 07/10/2015. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=235.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, Peters JA and Harmar AJ, CGTP Collaborators. (2013) The Concise Guide to PHARMACOLOGY 2013/14: Transporters. Br J Pharmacol. 170: 1706–1796.