Biochemical and Biophysical Research Communications
Functional analysis of ABCA8, a new drug transporter
Section snippets
Methods
Database screening for new member of ABC superfamily. We screened the GenBank database by the BLAST program using several known ABC transporters including the P-glycoprotein as the query. We found a Homo sapiens complete cDNA (AB020629, the mRNA of which is 5677 bp), which is now called ABCA8 by the HUGO (Human Gene Organization) Nomenclature Committee. This cDNA was obtained in pBluescript SK(−) from Kazusa DNA Research Institute (Kisarazu, Japan). The Kyte-Doolittle method predicted that the
Screening cDNA libraries
The complete Homo sapiens cDNA corresponding to the KIAA0822 protein (AB020629, 5677 bp mRNA) fulfilled the criteria of our screening. The cDNA was originally cloned as one of the full-length cDNAs with unknown function in human brain by Ohara and co-workers [8] from Kazusa DNA Research Institute (Kisarazu, Chiba, Japan) and registered in GenBank (with Accession No. AB020629). The gene is now called ABCA8 by the HUGO (Human Gene Organization) Nomenclature Committee. However, the function of this
Discussion
By screening an EST-database, we found KIAA0822 (now called ABCA8) as a possible new member of the ABC-transporter superfamily. This ABCA8 protein was shown to transport several drugs with a specificity substrate close to that of ABCC2/MRP-2 and of oatp, which does not belong to the ABC superfamily. The transport maximum is ATP-dependent. The Km of ABCA8 for the transport of [14C]estradiol-β-glucuronide was surprisingly low and similar to that of MRP-2/ABCC2 in Caco-2 cells [6], transfected
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