CLONING AND SEQUENCING OF 4 NEW MAMMALIAN MONOCARBOXYLATE TRANSPORTER(MCT) HOMOLOGS CONFIRMS THE EXISTENCE OF A TRANSPORTER FAMILY WITH ANANCIENT PAST

Measurement of monocarboxylate transport kinetics in a range of cell t ypes has provided strong circumstantial evidence for a family of monoc arboxylate transporters (MCTs). Two mammalian MCT isoforms (MCT1 and M CT2) and a chicken isoform (REMP or MCT3) have already been cloned, se quenced and expressed, and another MCT-like sequence (XPCT) has been i dentified. Here we report the identification of new human MCT homologu es in the database of expression sequence tags and the cloning and seq uencing of four new full-length MCT-like sequences from human cDNA lib raries, which we have denoted MCT3, MCT4, MCT5 and MCT6. Northern blot ting revealed a unique tissue distribution for the expression of mRNA for each of the seven putative MCT isoforms (MCT1-MCT6 and XPCT). All sequences were predicted to have 12 transmembrane (TM) helical domains with a large intracellular loop between TM6 and TM7. Multiple sequenc e alignments showed identities ranging from 20% to 55%, with the great est conservation in the predicted TM regions and more variation in the C-terminal than the N-terminal region. Searching of additional sequen ce databases identified candidate MCT homologues from the yeast Saccha romyces cerevisiae, the nematode worm Caenorhabditis elegans and the a rchaebacterium Sulfolobus solfataricus. Together these sequences const itute a new family of transporters with some strongly conserved sequen ce motifs, the possible functions of which are discussed.