Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily

The MRP subfamily of ABC transporters currently consists of at least six me mbers, several of which have been demonstrated to transport amphipathic ani ons and to confer in vitro resistance to chemotherapeutic agents. In search ing the data bases we identified the product of a cDNA sequencing project t hat bears significant similarity to MRP subfamily transporters. In this rep ort the predicted coding sequence, protein product and expression pattern o f this cDNA, termed MRP7, are analyzed. The MRP7 cDNA sequence encodes a 14 92 amino acid ABC transporter whose structural architecture resembles that of MRP1, MRP2, MRP3, and MRP6, in that its transmembrane helices are arrang ed in three membrane spanning domains. However, in contrast to the latter t ransporters, a conserved N-linked glycosylation site is not found at the N- terminus of MRP7. Comparisons of the MRP7 amino acid sequence indicated tha t while it is most closely related to other MRP subfamily members, its degr ee of relatedness is the lowest of any of the known MRP-related transporter s. The integrity of the predicted MRP7 coding sequence was confirmed by the synthesis of a similar to 158 kDa protein in reticulocyte lysates programm ed with the MRP7 cDNA. While MRP7 transcript was detected in a variety of t issues by RT/PCR, it was not readily detectable by RNA blot analysis, sugge sting that it is expressed at low levels in these tissues. Fluorescence in situ hybridization indicated that MRP7 maps to chromosome 6p12-21, in proxi mity to several genes associated with glutathione conjugation and synthesis . On the basis of these findings and evolutionary cluster analysis, we conc lude that MRP7 is a member of the MRP subfamily of amphipathic anion transp orters. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.