spans on a 120 kb genomic fragment; separated from MDR3 gene (which is transcribed in the same direction) by only 34 kb of intergenic DNA

5 kb mRNA

the protein is called P-glycoprotein; 170 kDa transmembrane glycoprotein which includes 10-15 kDa of N-term glycosylation; the N-term half of the molecule contains 6 transmembrane domains, followed by a large cytoplasmic domain with an ATP binding site, and then a second section with 6 transmembrane domains and an ATP binding site which shows over 65% of amino acid similarity with the first half of the polypeptide

normally expressed at secretory surface of a number of tissues, including biliary canaliculi, proximal tubules of the kidney, intestinal and colonic epithelium; hematopoietic stem cells express high levels of P-glycoprotein; overexpressed in many multidrug resistant cell lines and in tumor cells resistant to chemotherapy

mainly at the cell membrane, with a secondary localisation at the Golgi apparatus

the P-glycoprotein is an energy-dependent efflux pump involved in extrusion of many types of lypophilic coumpounds; it may acts in normal tissues as a protective mechanism against noxious xenobiotics and as a transporter of endogenous substrates; in tumour cells, the drug efflux pump results in a decrease in intracellular drug concentration

closely related gene to MDR3 (also called PGY3), located at the same chromosomal site but not implicated in multidrug resistance; there are 3 murine homolog genes (mdr1, mdr2, mdr3) out of which only 2 (mdr1 and mdr3) are involved in multidrug resistance; member of a large superfamily of transmembrane transporter proteins named ATP Binding Cassette (ABC) transporters or Traffic ATPases; structural homology with other ABC transporter proteins (CFTR, MRP)