Major Facilitator Superfamily Domain-containing Protein

Major facilitator superfamily domain-containing protein (MFSD) is a superfamily of membrane transport proteins which is universally known as a second transporter found in a variety of organisms. The transport proteins possess 12 transmembrane helices with a central substrate-binding pocket that determine the specificity of substrates transported. They can transport small solutes across the cell membrane using the already-existing electrochemical gradient, without directly using ATP hydrolytic energy. MFSD is identified as sugar transporters initially. However, following studies reveal that MFSD can act as transporters of a great diversity of substrates, such as small oxyanions, nutrients, drugs, neurotransmitters, and metabolites. MFSD plays a very important role in many biological processes. For example, the MFSD members expressed in the brain contribute to moving nutrients across the blood-brain barrier and clearing neurotransmitters from the synaptic cleft blocking neuronal transmission. Moreover, they function as drug transporters to move the drugs to the specific pathological parts.

There are about 430 MFSD proteins that are divided into solute carriers (SLCs) families and atypical MFS transport families (AMTFs). Here shows part of AMTFs in humans including sodium-dependent lysophosphatidylcholine symporter 1, sphingosine-1-phosphate transporter, sodium-dependent glucose transporter 1, molybdate-anion transporter, ceroid-lipofuscinosis neuronal protein 7. These AMTFs members are associated with the transportation of specific substrates. For example, MFSD4B functions as transport of glucose, bile salts and organic acids, metal ions and amine compounds. While MFSD2B specifically mediates export of sphingosine-1-phosphate in red blood cells and platelets. However, the substrate transported by MFSD8 is not clear.

Human AMTFs Members
MFSD2A	MFSD2B	MFSD4B	MFSD5	MFSD8

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