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2.A.125 The Eukaryotic Riboflavin Transporter (E-RFT) Family

Human and rat plasma membrane riboflavin transporters, hRFT1 and rRFT1, were identified on the basis of a rat kidney mRNA expression database (Horiba et al. 2004). hRFT1 and rRFT1 cDNAs have an open reading frame encoding 448- and 450-amino acid proteins, respectively. Overexpression of hRFT1 or rRFT1 increased the cellular accumulation of [(3)H]riboflavin (Yonezawa et al. 2008). The transfection of small interfering RNA targeting both hRFT1 and hRFT1sv significantly decreased the uptake of [(3)H]riboflavin by HEK-293 and Caco-2 cells. Riboflavin (Km ≈ 40μM) transport is Na+, potential, and pH independent. RFT1 shows low similarity with the TRAP-T porters (2.A.56), nucleoside transporters (2.A.57) and aromatic acid porters (2.A.1.15).

The generalized reaction catalyzed by RFT1 is:

riboflavin (out) ⇌ riboflavin (in)

This family belongs to the: Major Facilitator (MFS) Superfamily.

References associated with 2.A.125 family:

Ben Mariem, O., S. Saporiti, U. Guerrini, T. Laurenzi, L. Palazzolo, C. Indiveri, M. Barile, E. De Fabiani, and I. Eberini. (2023). In silico investigation on structure-function relationship of members belonging to the human SLC52 transporter family. Proteins 91: 619-633. 36511838
Ericsson, T.A., Y. Takeuchi, C. Templin, G. Quinn, S.F. Farhadian, J.C. Wood, B.A. Oldmixon, K.M. Suling, J.K. Ishii, Y. Kitagawa, T. Miyazawa, D.R. Salomon, R.A. Weiss, and C. Patience. (2003). Identification of receptors for pig endogenous retrovirus. Proc. Natl. Acad. Sci. USA 100: 6759-6764. 12740431
Horiba, N., S. Masuda, A. Takeuchi, H. Saito, M. Okuda, and K. Inui. (2004). Gene expression variance based on random sequencing in rat remnant kidney. Kidney Int 66: 29-45. 15200410
O''Callaghan, B., A.M. Bosch, and H. Houlden. (2019). An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency. J Inherit Metab Dis. [Epub: Ahead of Print] 30793323
Qiao, Y., Y. Cui, Y. Tan, C. Zhuang, X. Li, Y. Yong, X. Zhang, X. Ren, M. Cai, J. Yang, Y. Lang, J. Wang, C. Liang, and J. Zhang. (2024). Fluoride induces immunotoxicity by regulating riboflavin transport and metabolism partly through IL-17A in the spleen. J Hazard Mater 476: 135085. 38968825
Sabui, S., V.S. Subramanian, Q. Pham, and H.M. Said. (2019). Identification of transmembrane protein 237 as a novel interactor with the intestinal riboflavin transporter-3 (RFVT-3): role in functionality and cell biology. Am. J. Physiol. Cell Physiol. [Epub: Ahead of Print] 30892938
Wolf, C.J.H., H. Venselaar, M. Spoelder, H. Beurmanjer, A.F.A. Schellekens, and J.R. Homberg. (2023). An Overview of the Putative Structural and Functional Properties of the GHBh1 Receptor through a Bioinformatics Approach. Life (Basel) 13:. 37109455
Yao, Y., A. Yonezawa, H. Yoshimatsu, S. Masuda, T. Katsura, and K. Inui. (2010). Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. J Nutr 140: 1220-1226. 20463145
Yonezawa, A. and K. Inui. (2013). Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52. Mol Aspects Med 34: 693-701. 23506902
Yonezawa, A., S. Masuda, T. Katsura, and K. Inui. (2008). Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. Am. J. Physiol. Cell Physiol. 295: C632-641. 18632736