ABCMdb

ABCC5 p.Ala1239Thr

Predicted by SNAP2:	C: N (78%), D: D (80%), E: D (75%), F: D (80%), G: D (53%), H: D (71%), I: D (66%), K: D (80%), L: D (66%), M: D (63%), N: D (66%), P: D (80%), Q: D (66%), R: D (75%), S: N (82%), T: N (57%), V: N (72%), W: D (80%), Y: D (80%),
Predicted by PROVEAN:	C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: N, T: D, V: D, W: D, Y: D,

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Publications
[hide] A molecular understanding of ATP-dependent solute ... Cancer Metastasis Rev. 2007 Mar;26(1):15-37. Chang XB
A molecular understanding of ATP-dependent solute transport by multidrug resistance-associated protein MRP1.
Cancer Metastasis Rev. 2007 Mar;26(1):15-37., [PMID:17295059]

Abstract [show]
Over a million new cases of cancers are diagnosed each year in the United States and over half of these patients die from these devastating diseases. Thus, cancers cause a major public health problem in the United States and worldwide. Chemotherapy remains the principal mode to treat many metastatic cancers. However, occurrence of cellular multidrug resistance (MDR) prevents efficient killing of cancer cells, leading to chemotherapeutic treatment failure. Numerous mechanisms of MDR exist in cancer cells, such as intrinsic or acquired MDR. Overexpression of ATP-binding cassette (ABC) drug transporters, such as P-glycoprotein (P-gp or ABCB1), breast cancer resistance protein (BCRP or ABCG2) and/or multidrug resistance-associated protein (MRP1 or ABCC1), confers an acquired MDR due to their capabilities of transporting a broad range of chemically diverse anticancer drugs. In addition to their roles in MDR, there is substantial evidence suggesting that these drug transporters have functions in tissue defense. Basically, these drug transporters are expressed in tissues important for absorption, such as in lung and gut, and for metabolism and elimination, such as in liver and kidney. In addition, these drug transporters play an important role in maintaining the barrier function of many tissues including blood-brain barrier, blood-cerebral spinal fluid barrier, blood-testis barrier and the maternal-fetal barrier. Thus, these ATP-dependent drug transporters play an important role in the absorption, disposition and elimination of the structurally diverse array of the endobiotics and xenobiotics. In this review, the molecular mechanism of ATP-dependent solute transport by MRP1 will be addressed.

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No. Sentence Comment
143 Converting the mouse Mrp1 A1239 to human T at the corresponding position (mouse Mrp1/ A1239T) created a protein that increased E217βG transport 3-fold, but decreased resistance to vincristine and VP-16 without affecting anthracycline resistance [85]. Login to comment
144 Interestingly, substitution of a second murine sequence in Mrp1/ A1239T with a human MRP1 codon to generate the Mrp1/ A1239T/Q1086E double mutant restored the resistance to both vincristine and VP-16 [85]. Login to comment