ABCMdb

ABCB4 p.Phe165Ile

None has been submitted yet.

Publications

PMID: 17562004 [PubMed] Rosmorduc O et al: "Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene."

No. Sentence Comment

49 The Phe165Ile mutation was localized in the same part of this intracellular loop and may therefore give rise to a similar defect. Login to comment

PMID: 16622704 [PubMed] Oude Elferink RP et al: "Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein)."

No. Sentence Comment

141 Canalicular lipid transport defects can cause gallstone formation Cholesterol supersaturation of bile, which occurs in a large proportion of humans, leads to the formation of cholesterol Walker B; L556R 571del Truncation PFIC3 LPAC ICP 27 splice Truncation 132 del Truncation TM 2; W138R TM 12; 981 del Truncation Linker; Q636X Truncation TM 11; R957X Truncation TM 6; S346I E395G Walker B; I541F TM 12; G983S Walker A; V425M Walker A; T424A Walker B; D564G TM 7; F711S 180 del truncation 336 delT truncation Exon 22-23 del truncation F165I T175A TM 5; M301T TM 5; S320F 336 insT truncation Walker A; 432 insA truncation E528D L591Q W658stop 757 insT R788E A934T P1161S TM 5; S320F TM 8; G762ER144X Walker B; A546D Walker B; G535AALL 96 del Truncation Walker B; L556R 571del Truncation PFIC3 LPAC ICP 27 splice Truncation 132 del Truncation TM 2; W138R TM 12; 981 del Truncation Linker; Q636X Truncation TM 11; R957X Truncation TM 6; S346I E395G Walker B; I541F TM 12; G983S Walker A; V425M Walker A; T424A Walker B; D564G TM 7; F711S 180 del truncation 336 delT truncation Exon 22-23 del truncation F165I T175A TM 5; M301T TM 5; S320F 336 insT truncation Walker A; 432 insA truncation E528D L591Q W658stop 757 insT R788E A934T P1161S TM 5; S320F TM 8; G762ER144X Walker B; A546D Walker B; G535AALL 96 del Truncation Fig. 3 Summary of the known mutations and their localization in the protein, as identified in patients with PFIC type 3, LPAC syndrome (intrahepatic gallstone formation), and intrahepatic cholestasis of pregnancy (ICP). Login to comment

PMID: 12891548 [PubMed] Rosmorduc O et al: "ABCB4 gene mutation-associated cholelithiasis in adults."

No. Sentence Comment

68 ABCB4 Gene Mutations in Patients With LPAC Syndrome Gene position Location and nucleotide change Peptide change Protein domain Status 6 495T3A Phe165Ile First intracellular loop Heterozygous 523T3C Thr175Ala between TM2 and TM3 Heterozygous 9 902T3C Met301Thr TM5 Heterozygous 959C3T Ser320Phe TM5 Homozygous 10 1007-1015insT 355Stop TM6 Heterozygous 1007-1015delT 341Stop TM6 Heterozygous 12 1327insA 447Stop Close to NBD11 Heterozygous 14 1584G3C Glu528Asp Close to NBD11 Heterozygous 15 1772T3A Leu591Gln Third intracellular loop Homozygous 17 1973G3A Try658Stop Third intracellular loop linker domain Heterozygous 18 2270-2273insT 793Stop Fourth intracellular loop between TM8 and TM9 Heterozygous 19 2363G3T Arg788Glu Fourth intracellular loop between TM8 and TM9 Heterozygous 23 2800G3T Ala934Thr Fifth intracellular loop between TM10 and TM11 Homozygous 26 3481C3T Pro1161Ser Close to NBD2 Heterozygous NOTE. The A of ATG of the initiator Met codon was denoted as "nucleotide ϩ 1." Login to comment
98 The Phe165Ile mutation was localized in the same part of this intracellular loop and might thereby give rise to a similar defect. Login to comment

PMID: 24381502 [PubMed] Kim TH et al: "Functional Characterization of ABCB4 Mutations Found in Low Phospholipid-Associated Cholelithiasis (LPAC)."

No. Sentence Comment

8 Through a membrane vesicular transport assay, we observed that the uptake of paclitaxel was significantly reduced in membrane vesicles expressing 2 ABCB4 mutations, F165I and S320F. Login to comment
26 In this study, we selected 3 novel missense mutations of ABCB4 that were first reported by Rosmorduc et al. [3] and F165I 5`-AGG AAA TAG GAT GGA TTG ACA TCA ATG ACA-3` M301T 5`-GCA AAC ATT TCC ACG GGT ATT GCC TTS CTG-3` S320F 5`-AGG ACA CAA ATC AGA CAG CAT CAA AGG GAA-3` The SNP sites were marked by bold-faced letters with underlines. Login to comment
56 RESULTS Mutations of ABCB4 examined in this study To perform a molecular characterization of ABCB4 muta- cDNA position Amino acid substitution Predicted domain a c.495T&#ff1e;A F165I ICD1 c.902T&#ff1e;C M301T TM5 c.959C&#ff1e;T S320F TM5 Position of each mutant was based upon the translational start site. Login to comment
80 The ABCB4 mutant, F165I might be located in the ICD1, while other two mutants, M301T and S320F are located in the TM5 [3]. Login to comment
84 To exclude ATPase activity by other endogenous ABC transporters including MDR1, values for transport activity were obtained by subtracting the uptake in empty vector-transfected cells from that in cells transfected with ABCB4 reference or mutant-bearing vectors, at each corresponding paclitaxel concentration. The uptake of paclitaxel Vmax (nmol mg &#ff0d;1 per min) Km (mM) Vmax/Km ratio (nmol mg&#ff0d;1 min &#ff0d;1 per mM) Reference 28.98&#b1;1.565 1.114&#b1;0.1391 27.13&#b1;5.232 F165I 16.82&#b1;1.565* 1.028&#b1;0.1189 15.56&#b1;4.658* M301T 23.23&#b1;0.8641 1.206&#b1;0.2875 20.60&#b1;5.628 S320F 18.55&#b1;2.726* 1.185&#b1;0.1064 15.99&#b1;3.736* Data (mean&#b1;SD) are from 5 separate experiments. Login to comment
92 was significantly reduced in membrane vesicles expressing 2 ABCB4 mutations, F165I and S320F. Login to comment
95 We observed that the average values of Vmax/Km for F165I and S320F were significantly reduced compared to that of the ABCB4 reference. Login to comment
100 The 2 mutations, F165I and S320F that showed decreased transport activities as compared to the reference, had significantly decreased MDR3 expression as compared to reference. Login to comment
102 Then, we investigated MDR3 expression levels of these mutants on the plasma membrane by cell surface biotinylation and observed that those of F165I and S320F were significantly decreased by 31%, compared to that of the reference (Fig. 2B). Login to comment
103 The results from immunoblotting or cell surface biotinylation experiments could explain the reason of altered transport activities of ABCB4 mutants, F165I and S320F; the decreased transport activities of these mutants were due to the reduced expression of functional MDR3 on the plasma membrane. Login to comment
106 The subcellular expression of M301T was comparable with that of the reference while the co-localization of F165I and S320F with plasma membrane was decreased. Login to comment
115 Through a membrane vesicular transport assay using paclitaxel, we found that 2 mutants, F165I and S320F, showed significantly decreased transport activity compared to the reference (Fig. 1). Login to comment
116 F165I and S320F are located in the ICD1 and TM5 of MDR3, respectively, that might be involved in coupling the energy from ATP hydrolysis to substrate transport and the conformational change involved in substrate extrusion, respectively [3,15]. Login to comment
120 The reduced transport function of F165I and S320F mutants also might be due to the decreased expression of functional MDR3 on the plasma membrane (Fig. 2). Login to comment
125 2 mutants, F165I and S320F, examined in this study also showed decreased transport activity and protein expression, although the extent of reduction was less than that of I541F. Login to comment