InterPro domain: IPR011701

Among the different families of transporter, only two occur ubiquitously in all classifications of organisms. These are the ATP-Binding Cassette (ABC) superfamily and the Major Facilitator Superfamily (MFS). The MFS transporters are single-polypeptide secondary carriers capable only of transporting small solutes in response to chemiosmotic ion gradients [ 1 , 2 , 3 ].

The major facilitator superfamily (MFS) of membrane proteins represents the largest family of secondary transporters with members from Archaea to Homo sapiens. MFS proteins target a wide spectrum of substrates, including ions, carbohydrates, lipids, amino acids and peptides, nucleosides and other small molecules in both directions across the membrane, in many instances catalysing active transport by transducing the energy stored in an proton electrochemical gradient into a concentration gradient of substrate [ 4 ]. One remarkable characteristic of the MFS is the high sequence variety within the superfamily. The sequences identity ranges around 12-18% but regions of functional similarity (e.g., substrate- or H-binding sites) align for only very closely related MFS transporters. A hydrophobic amino acid content of 60-70% of most MFS members, high alfa-helix content and an inherent symmetry of the proteins with regard to helix kinks and bends provides nonspecific overlapping of residues and probably accounts for the reported similarities. Structure from representative members show 12 transmembrane sections (TMSs) surrounding a central cavity, forming a semi-symmetrical structure. MFS includes 105 families based on phylogenetic analysis, sequence alignments, overlap of hydropathy plots, compatibility of repeat units, similarity of complexity profiles of transmembrane segments, shared protein domains and 3D structural similarities between transport proteins [ 5 ].

1. Major facilitator superfamily. Microbiol. Mol. Biol. Rev. 62, 1-34
2. Sugar transporters from bacteria, parasites and mammals: structure-activity relationships. Trends Biochem. Sci. 23, 476-81
3. Expansion of the Major Facilitator Superfamily (MFS) to include novel transporters as well as transmembrane-acting enzymes. Biochim Biophys Acta Biomembr 1862, 183277
4. Evolutionary mix-and-match with MFS transporters. Proc. Natl. Acad. Sci. U.S.A. 110, 5870-4