ABCMdb

ABCC1 p.Lys319Asp

None has been submitted yet.

Publications

PMID: 15155831 [PubMed] Haimeur A et al: "Mutations of charged amino acids in or near the transmembrane helices of the second membrane spanning domain differentially affect the substrate specificity and transport activity of the multidrug resistance protein MRP1 (ABCC1)."

No. Sentence Comment

48 The sequences of the individual sense strands (with the corresponding amino acid changes indicated in parentheses, the altered codons underlined, and silent mutations introducing new restriction sites italicized) were as follows: K(D)332K, 5Ј-G AGC TTC TTC TTC AAG GCC ATC CAC GAC CTG-3Ј; K332R, 5Ј-G AGC TTC TTC TTC AGG GCC ATC CAC GAC CTG-3Ј; D(K)336E, 5Ј-C AAG GCC ATC CAC GAG CTC ATG ATG TTT TCC-3Ј; D336K, 5Ј-C AAG GCC ATC CAC AAG CTT ATG ATG TTT TCC-3Ј; K332D/D336K, 5Ј-GC TTC TTC TTC GAC GCC ATC CAC AAA CTG ATG ATG-3Ј; K319D, 5Ј-G TTT AAG GTG TTA TAC GAC ACG TTT GGG CCC-3Ј; K347D, 5Ј-GGG CCG CAG ATA TTA GAC TTG CTC ATC AAG-3Ј; K347L, 5Ј-GGG CCG CAA ATC TTA CTT TTG CTC ATC AAG-3Ј; D360K, 5Ј-GAC ACG AAG GCG CCA AAG TGG CAG GGC TAC-3Ј; R394D, 5Ј-C GTC AGT GGC ATG GAG ATC AAG ACC GCT GTC-3Ј; R394I, 5Ј-C GTC AGT GGC ATG ATC ATC AAG ACC GCT GTC-3Ј; K396E, 5Ј-GT GGC ATG AGG ATC GAG ACC GCT GTC ATT GGG-3Ј; K396I, 5Ј-GT GGC ATG AGG ATC ATC ACC GCT GTC ATT GGG-3Ј; K(E)396R, 5Ј-GGC ATG AGG ATC AGG ACC GCT GTC ATT GGG GC-3Ј; D430K, 5Ј-C AAC CTC ATG TCT GTG AAG GCT CAG AGG Fig. 1. Login to comment
136 Lys319 was replaced with Asp (K319D), and Lys347 was replaced with Asp (K347D) as well as Leu (K347L). Login to comment
138 Thus the ability of the K319D, K347D, and K347L mutants to transport GSH was reduced by approximately 50% (Fig. 4C), whereas the transport of four other substrates (LTC4, E217betaG, E13SO4 and MTX) by these mutants remained comparable with wild-type MRP1 (Table 2). Login to comment
148 MRP1 Mutant % Wild-Type MRP1 Transport Activity LTC4 GSH E217betaG E13SO4 MTX TM6 K332D Ͻ10 Ͻ10 100 100 100 K332R 40 20 100 100 100 D336K Ͻ10 Ͻ10 Ͻ10 15 45 D(K)336E 20 Ͻ10 25 25 45 K332D/D336K Ͻ10 Ͻ10 30 25 50 K319D 100 50 100 100 100 K347D 100 45 100 100 100 TM7 D360K 100 100 100 100 100 R394D 100 100 100 100 100 K396E 25 50 25 25 35 K(E)396R 100 100 100 100 100 TM8 D436K 40 30 20 30 55 D(K)436E 100 100 100 100 100 ECL5/TM11 D572R 100 100 100 100 100 E573R 100 100 100 100 100 D578R 100 100 100 100 100 R593E 35 30 Ͻ10 Ͻ10 40 R(E)593K 100 100 100 100 100 or substrate specificity of MRP1. Login to comment
177 C, apigenin-stimulated [3 H]GSH uptake at 20 min by wild-type (WT) MRP1 (f), mutants K319D, K347D, and K347L (u), and empty pcDNA3.1(-) vector control (Ⅺ). Login to comment

PMID: 15161912 [PubMed] Leslie EM et al: "Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required."

No. Sentence Comment

69 MRP1 and MRP2 Expression Vectors and Transfections in HEK293T Cells-The construction and expression of wild-type MRP1 (WT-MRP1), wild-type MRP2 (WT-MRP2), and the MRP1 mutants K332L, D336K, K319D, and K347D in HEK293T cells have been described previously (31, 35-37). Login to comment
204 To determine whether these amino acid residues are critical for transport of As(GS)3, transport assays were done using membrane vesicles prepared from HEK293T cells transfected with pcDNA3.1(-) (empty vector), WT-MRP1, D336K-MRP1, K332L-MRP1, K319D-MRP1, and K347D-MRP1 cDNAs. Login to comment
207 Despite the fact that K319D-MRP1 and K347D-MRP1 have a selectively decreased ability to transport GSH, these mutants transported As(GS)3 at levels similar to WT-MRP1. Login to comment
222 As(GS)3 transport by wild-type and mutant K332L, D336K, K319D, K347D-MRP1. Login to comment
223 A, membrane vesicles prepared from HEK293T cells transfected with empty vector (pcDNA3.1(-)), wild-type MRP1 (WT-MRP1), or mutant MRP1 (K332L-MRP1, D336K-MRP1, K319D-MRP1, or K347D-MRP1) were immunoblotted with the MRP1-specific mAb QCRL-1 as described under "Experimental Procedures." Login to comment