The ATP-binding cassette (ABC) gene family encodes a diverse group of transporter proteins that pump a wide variety of compounds across the membranes of cells and tissues. Several human ABC transporters are overexpressed in tumor cells that are resistant to chemotherapy drugs. In addition, several ABC genes (CFTR, SUR, ALDP) are mutated in inherited diseases. The ABCG2 (MXR/ABCP/BCRP) gene is overexpressed in tumor cell lines that are resistant to mitoxantrone, topotecan and several other drugs. Analysis of the gene in resistant cell lines demonstrates that alterations at amino acid 482 confer selectivity of the pump to rhodamine and other drugs. Characterization of the human genome sequence demonstrates that there are only 48 human ABC genes, divided into 7 subfamilies. In contrast Drosophila has 55 genes. Evolutionary analysis demonstrates that rapid birth and death of genes has occurred since insects and vertebrates had a common ancestor. The human ABCG5 and ABCG8 genes are highly expressed in the liver and intestine and are mutated in sitosterolemia, a sterol transport disorder. Analysis of a cluster of 5 ABCA genes on human chromosome 17 and mouse chromosome 11 reveals that these genes have identical genomic structures but unique tissue expression patterns. There have been two gene duplication and loss events in this cluster between the human and mouse lineage.
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