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)
References:
The riboflavin (Km = 40μM) transporter, RFT1, SLC52A1, of 448 aas and 11 TMSs in a 6 + 5 TMS arrangement (Yonezawa et al. 2008). The C-terminal 150 aas are 92% identical to porcine endogenous retrovirus A receptor 2 (PERV-A receptor 2) and 57% identical to the G-protein-coupled receptor 172A (XP_001519123).RFT1 is also a viral receptor, and the putative structural and functional properties of the GHBh1 receptor have been summarized (Wolf et al. 2023). Vitamin B2/riboflavin transporters play key roles in biochemical oxidation-reduction reactions of carbohydrate, lipid, and amino acid metabolism (Yonezawa et al. 2008, Yao et al. 2010). It may function as a cell receptor for retroviral envelopes similar to the porcine endogenous retrovirus (PERV-A) (Ericsson et al. 2003). The SLC52 family includes RFVT1-3, mutations in which are associated with two diseases, MADD and the Brown-Vialetto-Van Laere syndrome (Ben Mariem et al. 2023). Structure-function relationships have been reported (Ben Mariem et al. 2023).
Animals
RFT1 of Homo sapiens (B5MEV1)
Solute carrier family 52, riboflavin transporter, member 3 (Riboflavin transporter 2) (hRFVT2, RFVT3). Riboflavin transporter deficiency (RTD) is a rare neurological condition that encompasses the Brown-Vialetto-Van Laere and Fazio-Londe syndromes. Since the discovery of pathogenic mutations in the SLC52A2 and SLC52A3 genes that encode human riboflavin transporters RFVT2 and RFVT3, treatment with high doses of riboflavin have proven to be helpful treatments. Patients exhibit a deteriorating progression of peripheral and cranial neuropathy that causes muscle weakness, vision loss, deafness, sensory ataxia, and respiratory compromise which when left untreated can be fatal (O'Callaghan et al. 2019). Intestinal RFVT3 interacts with TMEM237 (TC# 8.A.121), and this interaction has physiological/biological significance; it seems to be an inducer of RFVT3 synthesis (Sabui et al. 2019). Fluoride induces immunotoxicity by regulating riboflavin transport and metabolism partly through IL-17A in the spleen (Qiao et al. 2024).
Animals
SLC52A3 of Homo sapiens
Solute carrier family 52, riboflavin transporter, member 2 (Porcine endogenous retrovirus A receptor 1) (PERV-A receptor 1) (Protein GPR172A) (Riboflavin transporter 2) (hRFVT2) (Yonezawa and Inui 2013). Riboflavin transporter deficiency (RTD) is a rare neurological condition that encompasses the Brown-Vialetto-Van Laere and Fazio-Londe syndromes since the discovery of pathogenic mutations in the SLC52A2 and SLC52A3 genes that encode human riboflavin transporters RFVT2 and RFVT3. Patients exhibit a deteriorating progression of peripheral and cranial neuropathy that causes muscle weakness, vision loss, deafness, sensory ataxia, and respiratory compromise which when left untreated can be fatal (O'Callaghan et al. 2019).
Animals
SLC52A2 (RFVT2) of Homo sapiens
Uncharacterized protein of 701 aas and 11 TMSs.
UP of Vitrella brassicaformis
Uncharacterized protein of 561 aas and 11 TMSs.
UP of Naegleria gruberi (Amoeba)