2.A.48.1.1
Folate/folate derivative transporter, RFC1. Although oligomeric, each monomer provides the channel (Hou et al., 2010). It is downregulated in Chronic Kidney Disease (CKD) in heart, liver, and brain, causing malabsorption (Bukhari et al., 2011).  5-Aminoimidazole-4-carboxamide riboside (AICAR), an agent with diverse pharmacological properties, augments transport of folates and antifolates by promoting substrate:substrate antiport (Visentin et al. 2012).  Its role in antifolate cancer chemotherapy has been reviewed (Matherly et al. 2014).  In cats, this protein is the receptor for feline leukemia virus (feLV) (Miyake et al. 2019). The R27H polymorphism affects the secondary and tertiary structures of SLC19A1 with a loss of ligand-binding sites (Naushad et al. 2019). 2'3'-cyclic-GMP-AMP (cGAMP), a second messenger that activates the antiviral stimulator of IFN genes (STING), elicits an antitumoral immune response. SLC19A1 is an importer that transports extracellular cGAMP into the cytosol (Li et al. 2022), and binding of cyclic dinucleotides has been demonstrated (Zhang et al. 2022). Folate supplementation has been reviewed (He and Li 2023). FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of methotraxate (MTX), whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells (Bai et al. 2024). Import of extracellular 2'-3'cGAMP occurs via the folate transporter, SLC19A1, and this establishes an antiviral response that limits herpes simplex virus-1 (Szemere and Murphy 2024).