MONOCARBOXYLATE TRANSPORTERS - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 149

MCT2 MCT1

MCT3
MCT4

MCT6

MCT12

MCT11

MCT13

TAT 1
MCT8

MCT5

MCT7

MCT14

MCT9

FIGURE 7.1. Phylogentic relationship predicted among all SLC family members. A Newick
string containing all 14 protein sequences was generated using the ClustalW algorithm and
plotted as a radial tree using T-REX software (freely available from http://www.labunix.uqam
.ca/ ∼ makarenv/trex.html).

that these residues are critical for the proper association of MCT1 with its ancillary
protein CD147. Finally, experiments suggest that R143 and K142 may be involved in
the stereospecificity of MCT1. 9 The hypothetical protein structure of MCT1 (Figure
7.2) based on the crystal structure of the Escherichia coli lactose permease protein
illustrates the position of the critical amino acids. It is evident that the predicted
positions of the amino acids necessary for substrate binding do indeed face the putative
translocation pore.

7.1.2. SLC5 Gene Family: SMCTs

The recent identification of a mutation in a sodium-dependent butyrate transporter
associated with colon cancer led to the discovery of a set of sodium-dependent MCTs
that transport monocarboxylates with a high degree of specificity but do not exhibit the
typical gene or protein structure common to the SLC16 transporter family. 10 − 12 These
transporters,

denoted sodium-coupled monocarboxylate transporters (SMCTs),