Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins.
The complete nucleotide and primary structure (1276 amino acids) of a full length mdr cDNA capable of conferring a complete multidrug-resistant phenotype is presented. The deduced amino acid sequence suggests that mdr is a membrane glycoprotein which includes six pairs of transmembrane domains and a cluster of potentially N-linked glycosylation sites near the amino terminus. A striking feature of the protein is an internal duplication that includes approximately 500 amino acids. Each duplicated segment includes a consensus ATP-binding site. Amino acid homology is observed between the mdr gene and a series of bacterial transport genes. This strong homology suggests that a highly conserved functional unit involved in membrane transport is present in the mdr polypeptide. We propose that an energy-dependent transport mechanism is responsible for the multidrug-resistant phenotype.
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D001693:Biological Transport, Active; D004247:DNA / Q000032:analysis*; D004351:Drug Resistance / Q000235:genetics*; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics; D008322:Mammals; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics; D010455:Peptides / Q000032:analysis; D010641:Phenotype
D001426:Bacterial Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D004247:DNA