Gene Mapping, Cloning and Sequencing Cytogenet Cell Genet 92:204–208 (2001) An ATP-binding cassette gene (ABCG5) from the ABCG (White) gene subfamily maps to human chromosome 2p21 in the region of the Sitosterolemia locus S. Shulenin, a L.M. Schriml, a A.T. Remaley, b S. Fojo, b B. Brewer, b R. Allikmets c and M. Dean a a Laboratory of Genomic Diversity, NCI-Frederick, Frederick MD; b National Heart, Lung and Blood Institute, Bethesda MD; c Departments of Ophthalmology and Pathology, Columbia University, New York NY (USA) Received 5 April 2000; revision accepted 23 October 2000. Request reprints from: Dr. Michael Dean, Laboratory of Genomic Diversity, NCI-Frederick, Bldg 560, Rm 21-18, Frederick MD 21702 (USA); telephone: 301-846-5931; fax: 301-846-1909; email: dean@ncifcrf.gov Current address of L.M.S.: National Center for Biotechnology Information, Bethesda MD (USA). ABC Fax + 41 61 306 12 34 E-mail karger@karger.ch www.karger.com © 2001 S. Karger AG, Basel 0301–0171/01/0924–0204$17.50/0 Accessible online at: www.karger.com/journals/ccg Abstract. We characterized a new human ATP-binding cas- sette (ABC) transporter gene that is highly expressed in the liv- er. The gene, ABCG5, contains 13 exons and encodes a 651 amino acid protein. The predicted protein is closely related to the Drosophila white gene and a human gene, ABCG1, which is induced by cholesterol. This subfamily of genes all have a single ATP-binding domain at the N-terminus and a single C-termi- nal set of transmembrane segments. ABCG5 maps to human chromosome 2p21, between the markers D2S117 and D2S119. The abundant expression of this gene in the liver suggests that the protein product has an important role in transport of spe- cific molecule(s) into or out of this tissue. Copyright © 2001 S. Karger AG, Basel ABC proteins bind and hydrolyze ATP providing energy for the transport of an array of substrates (Dean and Allikmets, 1995). Several ABC genes are exclusively expressed in the liver and are involved in the energy-dependent transport of bile salts and bile acids from the liver into the bile (Muller and Jansen, 1998). For example the ABCC2 (MRP2) protein is involved in the elimination of amphipathic organic anions, ABCB4 (MDR3) mediates the secretion of phosphatidylcholine, and ABCB11 (SPGP/BSEP) transports taurocholate and other bile salts from the liver into the bile (Gerloff et al., 1998; Straut- nieks et al., 1998). The ABCA1 (ABC1) gene was recently shown to be mutated in Tangier disease, a disorder involving abnormal accumulation of cholesterol in macrophages and very low high-density lipoproteins (HDL) in the serum (Bodzioch et al., 1999; Brooks-Wilson et al., 1999; Remaley et al., 1999; Rust et al., 1999). Current models of ABCA1 function suggest that the gene is involved in the transfer of cholesterol from the plas- ma membrane to apolipoprein A molecules outside of the cell, to initiate HDL formation Eukaryotic ABC transporters are divided into seven distinct subfamilies based on phylogenetic analysis of the sequence of ATP-binding domains as well as the structure and arrangement of their domains (Allikmets et al., 1996; Decottignies and Gof- feau, 1997; Michaelis and Berkower, 1995). ABC proteins are either full size, as are ABCB11, ABCB1, ABCB4, and ABCC2, with approximately 12 transmembrane domains and two ATP binding sites on each molecule; or they are half size with six transmembrane domains and one ATP binding site, such as ABCG1. The half-transporters are presumably required to dimerize to form a functional transporter. While the best stud- ied half-transporters form heterodimers, homodimerization is certainly possible. Downloaded by: Kaohsiung Medical University Library 163.15.154.53 - 4/28/2018 2:15:50 PM