PROSITE documentation PDOC50850

Major facilitator superfamily (MFS) profile

Transporters can be grouped in two classes, primary and secondary carriers. The primary active transporters drive solute accumulation or extrusion by using ATP hydrolysis, photon absorption, electron flow, substrate decarboxylation or methyl transfer. If charged molecules are unidirectionally pumped as a consequence of the consumption of a primary cellular energy source, electron chemical potential results. This potential can than be used to drive the active transport of additional solutes via secondary carriers.

Among the different transporter the two largest families that occur ubiquitously in all classifications of organisms are the ATP-Binding Cassette (ABC) primary transporter superfamily (see <PDOC00185>) 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]. They function as uniporters, symporters or antiporters. In addition their solute specificity are also diverse. MFS proteins contain 12 transmembrane regions (with some variations).

The 3D-structure of human GLUT1, an archetype of the major facilitator superfamily has been solved (see <PDB:1JA5>) [3]. Helices 1-5, 8, 10-12 are arranged in a 9-member barrel-like manner, delimiting a hydrophilic central channel. Helix 7 is located in the center of the channel suggesting a role in regulating transport of solutes through the channel.

Some proteins known to belong to the MFS superfamily are listed below:

• Sugar transporters. The largest family, they can function by uniport, solute-solute antiport or solute-cation symport depending on the system or conditions (see <PDOC00190>).
• Drug:H+ antiporters or multidrug transporters. The extrusion of cytotoxic drugs from multidrug resistant cells by overexpressed multidrug transporter is an important cause of failure of the drug-based treatment of patient with cancers or infections by pathogenic microorganisms [4].
• Organophosphate:Pi antiporters (OPA). Small permeases restricted to bacteria.
• Oligosaccharide:H+ symporters (OHS). Permeases restricted to bacteria.
• Metabolite:H+ symporters (MHS).
• Nitrate/nitrite symporter (NNP). This family is present in bacteria, fungi and plants. It catalyzes either nitrate uptake or nitrite efflux.
• Phosphate:H+ symporters (PHS). It is present only in fungi and plants.
• Nucleoside:H+ symporters (NHS). Small permeases restricted to Gram-negative bacteria.
• Oxalate/formate antiporters (OFA). Present in bacteria, archaea and eukaryotes.
• Sialate:H+ symporters (SHS). Small permeases restricted to Gram-negative bacteria.
• Monocarboxylate porters (MCP).
• Anion:cation symporters (ACS).
• Aromatic acid:H+ symporters (AAHS). They transport a variety of aromatic acids as well as cis,cis-muconate. One member of this family (PCAK) serves as a chemoreceptor allowing the bacteria to swim up concentration gradiants of its substrate [5].
• Cyanate permeases (CP). Small bacterial proteins of around 400 residues.
• Proton-dependent oligopeptide transporters (POT). AAHS and POT are the most divergent MFS families.

The profile we developed covers the 12 transmembrane regions.