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 [2], 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]

Bharadwaj R, Lusi CF, Mashayekh S, Nagar A, Subbarao M, Kane GI, Wodzanowski KA, Brown AR, Okuda K, Monahan A et al.. (2023) Methotrexate suppresses psoriatic skin inflammation by inhibiting muropeptide transporter SLC46A2 activity. Immunity, [Epub ahead of print]. DOI: 10.1016/j.immuni.2023.04.001 [PMID:37116499]

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, 469 (1): 33-44. [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]