LITMIR.BIZ

Скачать книгу

ASBT SLC10A2 13q33 [40] BSEP ABCB11 2q24 [41] OST‐alpha SLC51A 3q29 [42] OST‐beta SLC51B 15q22.31 (Mapview) [42] P‐glycoprotein MDR1 ABCB1 7q21.1 [43] MDR3 ABCB4 7q21.12 [44] Multidrug resistance protein (MRP) MRP1 ABCC1 16p13.1 [45] MRP2 ABCC2 10q24 [46] MRP3 ABCC3 17q22 [47] MRP4 ABCC4 13q32 [48] MRP5 ABCC5 3q27 [49] MRP6 ABCC6 16p13.1 [50] MRP7 ABCC10 6p21.1 [51] MRP8 ABCC11 16q12.1 [52] MRP9 ABCC12 16q12.1 [52] Breast cancer resistance protein BCRP ABCG2 4q22 [53] Multidrug and toxin extrusion protein MATE1 SLC47A1 17p11.2 [54] MATE2 SLC47A2 17p11.2 [54] Monoamine transporters SERT SLC6A4 17q11.2 [55] NET SLC6A2 16q12.2 [56] Folate transporters RFT1 SLC19A1 21q22.3 [57] PCFT SLC46A1 17q11.2 [58]

      References listed above are those where the human chromosome locus were reported.

1.7 NOMENCLATURE OF DRUG TRANSPORTERS

The primary objective of this nomenclature is to provide a unifying system of assigning an unambiguous designation to each drug transporter gene and its protein, inclusive of the specific subclass to which it belongs. This book adopts the HUGO‐approved designations, which are used widely by the drug transporter communities. In general, the genes are named using the root symbol, e.g., SLC, followed by a numeral (e.g., SLC22, solute carrier family 22), followed by a letter that defines the subfamily (only A is used when the family has not been subdivided), and finally a number designating the individual transporter gene (e.g., SLC22A6). Transporters are assigned to a specific family if the encoded protein has at least 20% amino acid sequence identity to other members of that family. There is also naming difference between human and nonhuman species: For human gene, e.g., SLCO (all italicized, all capitalized), and for human protein, e.g., OATP (not italicized, all capitalized); For nonhuman gene, e.g., Slco (all italicized, only the initial letter is capitalized), and for nonhuman protein, e.g., Oatp (not italicized, only the initial letter is capitalized).

1.8 REGULATION OF DRUG TRANSPORTERS

      Giving the importance of drug transporters in the absorption, distribution, and excretion of a diverse array of environmental toxins and clinically important drugs, alteration in the function of these transporters plays a critical role in intra‐ and inter‐individual variability of the therapeutic efficacy and the toxicity of the drugs. As a result, the activity of drug transporters must be under tight regulation so as to carry out their normal duties. Key players involved in the regulation of transporters are hormones, protein kinases, nuclear receptors, scaffolding proteins, and disease conditions. These players may affect transporter activity at multiple levels, including (i) when and how often a gene encoding a given transporter is transcribed (transcriptional control), (ii) how the primary RNA transcript is spliced or processed (RNA processing control), (iii) which mRNA in the cytoplasm is translated by ribosomes (translational control), (iv) which mRNA is destabilized in the cytoplasm (mRNA degradation control), and (v) how a transporter is modified and assembled after it has been made (posttranslational control). Post‐translational modification may alter physical and chemical properties of the transporters, their folding, conformation, distribution, stability, and their activity. Because of such loops and layers of regulation, the functional diversity of

Скачать книгу