TAILIEUCHUNG - Báo cáo khoa học: ABCG transporters and disease

ATP-binding cassette (ABC) transporters form a large family of transmem-brane proteins that facilitate the transport of specific substrates across membranes in an ATP-dependent manner. Transported substrates include lipids, lipopolysaccharides, amino acids, peptides, proteins, inorganic ions, sugars and xenobiotics. | IFEBS Journal MINIREVIEW ABCG transporters and disease Owen M. Woodward1 Anna Kottgen2 3 and Michael Kottgen2 4 1 Department of Physiology Johns Hopkins University Schoolof Medicine Baltimore MD USA 2 RenalDivision University MedicalCentre Freiburg Freiburg Germany 3 Department of Epidemiology Johns Hopkins Bloomberg Schoolof Public Health Baltimore MD USA 4 Department of Nephrology Johns Hopkins University Schoolof Medicine Baltimore MD USA Keywords ABCG2 gout GWAS hyperuricemia urate Correspondence M. Kottgen RenalDivision University Medical Centre Freiburg Freiburg Germany Fax 49 0 761 27063240 Tel 49 0 761 27032990 E-mail Received 17 December 2010 revised 18 February 2011 accepted 6 May 2011 doi ATP-binding cassette ABC transporters form a large family of transmembrane proteins that facilitate the transport of specific substrates across membranes in an ATP-dependent manner. Transported substrates include lipids lipopolysaccharides amino acids peptides proteins inorganic ions sugars and xenobiotics. Despite this broad array of substrates the physiological substrate of many ABC transporters has remained elusive. ABC transporters are divided into seven subfamilies A-G based on sequence similarity and domain organization. Here we review the role of members of the ABCG subfamily in human disease and how the identification of disease genes helped to determine physiological substrates for specific ABC transporters. We focus on the recent discovery of mutations in ABCG2 causing hyperuricemia and gout which has led to the identification of urate as a physiological substrate for ABCG2. ABCG family Members of the ABCG family are half transporters with one ABC cassette in the amino terminus followed by six putative transmembrane domains see also reviews on other ABC transporters in the minireview series in this issue 1-3 . Full transporters contain two ABC cassettes and 12 transmembrane domains. Half .

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