Outside of the cell or into an extracellular compartment (endoplasmic reticulum, mitochondria, peroxisome). In eukaryotes, most ABC genes move compounds from the cytoplasm to the Sugars, vitamins, metal ions, etc.) into the cell. In bacteria, they are predominantly involved in the import of essential compounds that cannot be obtained by diffusion (e.g., In the cytoplasm and transfer the energy to transport the substrate across the membrane. The TM domains contain 6–11 membrane-spanning α-helices and provide the specificity for the substrate. The functional protein typically contains two NBFs and two transmembrane (TM) domains (Fig. ABC genes also contain an additional element, the signature C motif, located just upstream of the Walker B site ( Hyde et al. The NBFs contain characteristic motifs, Walker A and B, separated by ∼90–120 amino acids,įound in all ATP-binding proteins (Fig. Proteins are classified as ABC transporters based on the sequence and organization of their ATP-binding domains, also knownĪs nucleotide-binding folds NBFs. The transport of various molecules across all cell membranes ( Higgins 1992 Childs and Ling 1994 Dean and Allikmets 1995). These proteins bind ATP and use the energy to drive The ABC genes represent the largest family of transmembrane proteins. Previous Section Next Section ABC Protein and Gene Organization Will lead to important insights into the physiology and the molecular basis of many human disorders. Complete characterization of all ABC from the human genome and from model organisms The combined data enableĪn evolutionary analysis of the superfamily. In addition, theĪvailability of the complete Drosophila genome sequence allows the comparison of the known human ABC genes with those in the fly genome. We review the current state of knowledge on all human ABC genes in inherited disease and drug resistance. These dataĪllow predictions to be made as to potential functions or disease phenotypes associated with each protein. Map location on human chromosomes, expression data, and localization within the superfamily has been determined. PhylogeneticĪnalysis is used to divide all 48 known ABC transporters into seven distinct subfamilies of proteins. Has allowed the identification of new members of the superfamily based on nucleotide and protein sequence homology. Conservation of the ATP-binding domains of these genes Of human disorders with Mendelian and complex inheritance, including cystic fibrosis, neurological disease, retinal degeneration,Ĭholesterol and bile transport defects, anemia, and drug response. Genetic variation in these genes is the cause of or contributor to a wide variety ![]() The ATP-binding cassette (ABC) transporter superfamily contains membrane proteins that translocate a variety of substratesĪcross extra- and intra-cellular membranes.
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