Gene structures of the human non-neuronal monoamine transporters EMT and OCT2

Abstract.

Non-neuronal monoamine transporters OCT1, OCT2, and EMT, which are all members of the amphiphilic solute facilitator family, control signal transmission by removing released transmitters, such as dopamine, noradrenaline, adrenaline, 5-hydroxytryptamine, and histamine, from the extracellular space. In the current study, we have isolated human EMT (gene symbol SLC22A3) and OCT2 (SLC22A2) genes and report the gene and promoter organization. Both genes consist of 11 coding exons, with consensus GT/AG splice sites and conserved intron locations. The EMT gene is 77 kb, and the OCT2 gene is 45 kb in size. For the EMT gene, two transcription start points were identified by inverse polymerase chain reaction based on mRNA from Caki-1 cells. The EMT promoter, located within a CpG island, lacks a consensus TATA box but contains a prototypical initiator element and a number of potential binding sites for ubiquitous transcription factors Sp1 and NF-1. In contrast, the OCT2 promoter is not associated with a CpG island, contains a putative TATA box, and potential binding sites for specific transcription factors, such as HFH-8 and IK2. Since EMT and OCT2 may play important roles in catecholamine homeostasis and, as such, are candidate genes in human disease, the present results provide a basis for the analysis of genetic variation and the regulation of transcription.