Human SLC19A1 (RFC) knockout HEK-293T cell lysate

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

The Reduced Folate Carrier (RFC) also known as SLC19A1 functions as a bidirectional anion exchange transporter which facilitates the transport of folate and antifolate compounds across cellular membranes. This protein has a molecular mass of approximately 65 kDa. RFC achieves high expression levels in hematopoietic tissues the placenta and the choroid plexus indicating its critical role in tissues where folate demands are significant. Additionally its distribution in various cell types suggests it plays an essential role in folate homeostasis across the body.

Biological function summary

RFC operates as an important component of a membrane transport system that influences cellular folate uptake. It ensures an adequate supply of folate a vital nutrient for one-carbon metabolism linked to DNA synthesis repair and methylation processes. RFC functions independently not as a part of any larger protein complex but interacts with other cellular systems to maintain folate levels. Its activity significantly affects cellular proliferation because folate acts as a donor of methyl groups necessary for thymidine and purine biosynthesis critical precursors for DNA production.

Pathways

Folate transport by RFC supports essential pathways such as the tetrahydrofolate cycle and the methionine cycle. These pathways are indispensable for the synthesis of nucleotides and the regeneration of homocysteine to methionine impacting processes like DNA methylation and gene expression. In these pathways RFC operates in conjunction with proteins like methionine synthase and dihydrofolate reductase which further facilitate the folate cycle showing the protein's integration into cellular metabolism.

RFC influences conditions like acute lymphoblastic leukemia (ALL) and neural tube defects (NTDs). Altered RFC function or expression can affect folate homeostasis leading to impaired DNA synthesis and repair in rapidly dividing cells which is a characteristic of ALL. Furthermore insufficient folate transport through RFC can result in inadequate neural tube closure during fetal development related to NTDs. Associations with proteins like thymidylate synthase have shown RFC's role in antifolate drug resistance emphasizing its impact on cancer therapeutics.