Solute carrier family 46 member 1, also called Proton-coupled folate transporter, of the Major Facilitator Superfamily of transporters
Solute carrier family 46 member 1 (SLC46A1) is also called proton-coupled folate transporter (PCFT), G21, or heme carrier protein 1 (HCP1). It functions in two ways: as an intestinal proton-coupled high-affinity folate transporter that facilitates the absorption of folates across the brush-border membrane of the small intestine; and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithelial cells. It displays a higher affinity for folate than heme. It is also expressed in the choroid plexus and is required for transport of folates into the cerebrospinal fluid. Loss of function mutations in the SLC46A1 gene results in the autosomal recessive disorder "hereditary folate malabsorption" (HFM), characterized by severe systemic and cerebral folate deficiency. SLC46A1 belongs to the Eukaryotic Solute carrier 46 (SLC46)/Bacterial Tetracycline resistance (TetA) -like (SLC46/TetA-like) family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Feature 1:putative chemical substrate binding pocket [chemical binding site]
Evidence:
Comment:based on the structures of MFS transporters with bound substrates, substrate analogs, and/or inhibitors
Comment:since MFS proteins facilitate the transport of many different substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides, the residues involved in substrate binding may not be strictly conserved among superfamily members
Comment:the substrate binding site or translocation pore has access to both sides of the membrane in an alternating fashion through a conformational change of the MFS transporter
Jiyao W et al.(2023). "The conserved domain database in 2023.",