Identification of a novel human sterol-sensitive ATP-binding cassette transporter (ABCA7)

We report the identification of the full-length cDNA for a novel ATP-bindin g cassette (ABC) transporter from human macrophages. The mRNA is of 6.8 kb size and contains an open reading frame encoding a polypeptide of 2146 amin o acids with a calculated molecular weight of 220 kDa. The predicted protei n product is composed of two transmembrane domains and two nucleotide bindi ng folds indicating that it pertains to the group of full-size ABC transpor ters. The novel transporter shows highest protein sequence homology with th e recently cloned human cholesterol and phospholipid exporter ABCA1 (54%) a nd the human retinal transporter ABCR (49%), both members of the ABC transp orter subfamily A. In accordance with the currently proposed classification , the novel transporter was designated ABCA7. ABCA7 mRNA was detected predo minantly in myelo-lymphatic tissues with highest expression in peripheral l eukocytes, thymus, spleen, and bone marrow. Expression of ABCA7 is induced during in vitro differentiation of human monocytes into macrophages. In mac rophages, both the ABCA7 mRNA and protein expression are upregulated in the presence of modified low density lipoprotein and downregulated by HDL,. Ou r results suggest a role for ABCA7 in macrophage transmembrane lipid transp ort. (C) 2000 Academic Press.