ABCA6, a novel A subclass ABC transporter

Here we report the cDNA cloning of a novel member of the ABC A transporter subfamily from human macrophages. The identified coding sequence is of 5.0 kb size and contains an open reading frame which encodes a 1617 amino acid polypeptide. Structurally, the putative ABC transporter protein product con sists of two tandemly oriented subunits, each composed of a transmembrane d omain followed by a nucleotide binding fold, and thus conforms to the group of full-size ABC transporters. We also demonstrate the existence of an alt ernative transcript that codes for a 637 amino acid protein variant bearing the features of a truncated half-size transporter. Among the human ABC tra nsporter subfamily A the novel transporter shows highest protein sequence h omology with ABCA8 (60%), followed by ABCA2 (32%) and ABCA1 (32%), respecti vely. In agreement with the proposed classification, the novel transporter was designated ABCA6. The ABCA6 gene is ubiquitously expressed with highest mRNA levels in liver, lung, heart and brain. Analysis of the genomic organ ization demonstrated that the ABCA6 gene is composed of 38 exons which exte nd across a region of 62 kb size on chromosome 17q24.2. Based on its struct ural features and its cholesterol-responsive regulation ABCA6 is potentiall y involved in macrophage lipid homeostasis. (C) 2001 Academic Press.