Monocarboxylate transporters 9 and 14, and similar proteins of the Major Facilitator Superfamily of transporters
Monocarboxylate transporters 3 (MCT3) and 4 (MCT4) are also called Solute carrier family 16 members 8 (SLC16A8) and 3 (SLC16A3), respectively. They are proton-coupled transporters that facilitate the transport across the plasma membrane of monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and ketone bodies such as acetoacetate, beta-hydroxybutyrate and acetate. MCT3 is preferentially expressed in the basolateral membrane of the retinal pigment epithelium and plays a role in pH and ion homeostasis of the outer retina by facilitating the transport of lactate and H(+) out of the retina. Mice deficient with MCT3 display altered visual function. MCT4 is highly expressed in tissues dependent on glycolysis, and it plays an important role in lactate efflux from cells. MCT4 is expressed in neurons and astrocytes; it has been found to play a role in neuroprotective mechanism of ischemic preconditioning in animals (in the gerbil) with transient cerebral ischemia. Increased MCT4 expression has also been correlated with worse prognosis across many cancer types. MCT3/4 belongs to the Monocarboxylate transporter (MCT) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins. 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.",