Cloning and Characterization of Human Adenosine 5′-triphosphate-binding Cassette, Sub-family A, Transporter 2 (ABCA2)

We have isolated the full-length cDNA for human ATP-binding cassette, sub-family A, member 2 transporter ( ABCA2 ). The ORF of this cDNA encodes a protein consisting of 2436 amino acids with apparent molecular weight of M r 270,000. Accordingly, ABCA2 is the largest known mammalian ABC transporter described thus far. Analysis of mRNA expression levels indicated that ABCA2 is highest in human brain and has a broad expression pattern in a panel of tumor cell lines. Using specific antibodies to ABCA2 and various organelle marker proteins, ABCA2 was found to colocalize with the lysosomal/endosomal marker LAMP1, forming discrete, punctate intracellular vesicles. In ABCA2-transfected cells, the transporter also colocalized with a fluorescently labeled steroid analogue, estramustine. The sequestration of the steroid into the lysosomal/endosomal compartment indicates a potential substrate specificity for ABCA2. Furthermore, the presence of a lipocalin signature motif in the ABCA2 sequence suggests a possible broad role for this protein in the transport of steroids, lipids, and related molecules.