ABCMdb

ABCC3 p.Gln513Lys

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Publications

PMID: 18464048 [PubMed] Gradhand U et al: "Pharmacogenomics of MRP transporters (ABCC1-5) and BCRP (ABCG2)."

No. Sentence Comment

172 Figure 3 Predicted membrance topology of MRP3 (ABCC3) based on hydrophobicity analysis. Locations of the non-synonymous polymorphisms are indicated with arrows. See Table 3 for allele frequencies and description of funtional consequences. NH2 COOH NBD NBD in out Membrane Gly11Asp His68Tyr Ser346Phe Lys13Asn Gln513Lys Thr527Arg Ala528Gly Leu548Gln Gln741* Val799Met Gln933Arg_fs Ser1219Arg Arg1297His Pro1300Leu Leu1362Val Ala1398Val Thr1406Met Gly1423Arg Ala1513Asp MRP3 (ABCC3) NBD NBD Lys13Asn NBD NBD Lys13Asn In accordance with the latter finding, Gradhand et al. (2007b) found no impact of the -211C>T polymorphism on the ABCC3 promoter activity in transfected cell lines. Login to comment
174 For example, changing the tryptophan at position 1242 of MRP3 markedly altered the substrate specificity of MRP3 (Oleschuk et al., 2003), as is the case when a similar Table 3 MRP3 (ABCC3) single nucleotide polymorphisms. Location, allele frequency and functional effects. Position in coding sequence Amino acid exchange Location Allele frequency Effect NCBI ID ReferenceAf Ca Jp others 32G>A Gly11Asp Exon 1 - 0 [1] 0.6 [2] - - rs11568609 39G>C Lys13Asn Exon1 - 0.5 [1] 0 [3] - no effect on mRNA or protein in liver [1] 0 [2] 202C>T His68Tyr Exon2 - 1.6 [1] 0[3] 0 [2] - no effect on mRNA or protein in liver [1] 1037C>T Ser346Phe Exon9 - 0.5 [1] 0[3] 0 [2] - no effect on mRNA or protein in liver [1] 1537C>A Gln513Lys Exon12 - 0.5 [1] 0[3] 0 [2] - no effect on mRNA or protein in liver [1] 1580C>G Thr527Arg Exon 12 - - - - - rs1003354 1583C>G Ala528Gly Exon 12 - - - - - rs1003355 1643T>A Leu548Gln Exon 13 - 0.3 [4] 0 [3] 0 [2] - - 2221C>T Gln741* Exon 17 - 0 [1] 0.6 [2] - - 2395G>A Val799Met Exon 18 - 0 [1] 0.6 [2] - - 2798A-2799G del Gln933Arg_fs Exon 21 - 0 [1] 0.6 [2] - frame shift and early stop codon [2] 3657C>A Ser1219Arg Exon 25 - 0 [1] 1.1 [2] - no effect on expression, localization or transport in vesicles from transfected cells [4] 3890G>A Arg1297His Exon27 - 5.2 [1] 8 [4] 0 [3] 0 [2] - no effect on mRNA or protein in liver [1] 3899C>T Pro1300Leu Exon 27 - - - - - rs41280128 4084C>G Leu1362Val Exon 28 - - - - - rs1051625 4193C>T Ala1398Val Exon29 - - - - - rs11549764 4217C>T Thr1406Met Exon29 - 0 [1] 0.6 [2] - - 4267G>A Gly1423Arg Exon29 - 12.5 [1] 0 [3] - no effect on mRNA or protein in liver [1] 0 [2] 4538A>C Ala1513Asp Exon 31 - - - - - rs11656685 1. Login to comment

PMID: 18220559 [PubMed] Yu XQ et al: "Multidrug resistance associated proteins as determining factors of pharmacokinetics and pharmacodynamics of drugs."

No. Sentence Comment

406 MRP Chromosomal location Amino acid variation Nucleotide variation Location References Lys13Asn G39GC Exon1 His68Tyr C202T Exon2 Ser346Phe C1037T Exon9 Gln513Lys C1537A Exon12 Arg1297His G3890A Exon27 MRP3 17q21.3 Gly1423Arg G4267A Exon29 [241] MRP4 13q32.1 Unknown MRP5 3q27 Unknown L63L W64R 189G>C 190T>C Exon2 Exon2 [250] T364R Q378X 1091C>G 1132C>T Exon9 Exon9 [260, 261] R518X R518Q 1552 C>T 1553G>A Exon12 Exon12 [247, 262] R1141X R1138Q T1130M R1114C M1127T 3421C>T 3413G>A 3389C>T 3340C>T 3380C>T Exon24 Exon24 Exon24 Exon24 Exon24 [246, 247] R1275X 3823C>T Exon27 [246] P1346S 4036C>T Exon28 [246] MRP6 16p13.1 E1400K 4198G>A Exon29 [247] MRP7 6p12-21 Unknown MRP8 16q12.1 Unknown MRP9 16q12.1 Unknown CONCLUSIONS AND FUTURE DIRECTIONS MRPs which belong to the ABC transporter family are able to transport a remarkable array of diverse endo- and xenobiotics and their metabolites. Login to comment
360 The SNPs G39GC (allele frequency = 0.5%, in exon 1), C202T (1.6%, exon 2), C1037T (0.5%, exon 9), C1537A (0.5%, exon 12), G3890A (5.2%, exon 27) and G4267A (0.6%, exon 29) led to Lys13Asn, His68Tyr, Ser346Phe, Gln513Lys, Arg1297His and Gly1423Arg amino acid substitutions, respectively (Tablke 2). Login to comment

PMID: 20103563 [PubMed] Klaassen CD et al: "Xenobiotic, bile acid, and cholesterol transporters: function and regulation."

No. Sentence Comment

7118 Nucleotide Change Amino Acid Change In Vitro Function Protein Expression/Localization ABCC1 MRP1 G128C C43S 1↔ Intracellular C218T T73I 1↔ Normal C257T S92F 2↔ Normal C350T T117M 2↔ Normal G689A R230Q ↔ Normal G1057A V353M N.D. N.D. G1299T R433S 2↔ Normal G1898A R633Q 2↔ Normal G2012T G671V ↔ Normal G2168A R723Q 2 Normal G2965A A989T 2↔ Normal G3140C C1047S 1↔ Normal G3173A R1058Q ↔ Normal C4535T S1512L ↔ Normal ABCC2 MRP2 C-24T N.D. N.D. G1058A R353H N.D. N.D. G1249A V417I ↔ Normal C2366T S789F 12 Intracellular T2780G L927R N.D. N.D. C3298T R1100C N.D. N.D. G3299A R1100H N.D. N.D. T3563A V1188E N.D. N.D. G4348A A1450T ↔ Normal/Intracellular G4544A C1515Y N.D. N.D. ABCC3 MRP3 G32A G11D ↔ Normal C202T H68Y N.D. N.D. G296A R99Q N.D. Normal C1037T S346F 2 Normal C1537A Q513K N.D. N.D. T1643A L548Q N.D. N.D. G1820A S607N 2 Normal C2221T Gln741STOP N.D. N.D. G2293C V765L ↔ Normal G2395A V799M N.D. N.D. C2758T P920S 1 Normal G2768A R923Q 1 Normal C3657A S1219R N.D. N.D. C3856G R1286G ↔ Normal G3890A R1297H N.D. N.D. C4042T R1348C 1 Normal A4094G Q1365R ↔ Normal C4141A R1381S ↔ Intracellular C4217T T1406M N.D. N.D. G4267A G1423R N.D. N.D. ABCC4 MRP4 C52A L18I N.D. N.D. C232G P78A 2↔ Normal T551C M184T N.D. N.D. G559T G187W 2 Reduced A877G K293E ↔ Normal G912T K304N ↔ Normal C1067T T356M N.D. N.D. C1208T P403L 2↔ Normal G1460A G487E 2 Normal A1492G K498E ↔ Normal A1875G I625M N.D. N.D. C2000T P667L N.D. N.D. A2230G M744V ↔ Normal G2269A E757K N.D. Intracellular G2459T R820I N.D. N.D. G2560T V854F N.D. N.D. G2698T V900L N.D. N.D. G2867C C956S 1↔ Normal G3211A V1071I ↔ Normal C3425T T1142M N.D. N.D. G3659A R1220Q N.D. N.D. A3941G Q1314R N.D. N.D. 2, reduced function; 1, increased function; ↔, no change in function; N.D. not determined. Login to comment
7115 Nucleotide Change Amino Acid Change In Vitro Function Protein Expression/Localization ABCC1 MRP1 G128C C43S 1࢒ Intracellular C218T T73I 1࢒ Normal C257T S92F 2࢒ Normal C350T T117M 2࢒ Normal G689A R230Q ࢒ Normal G1057A V353M N.D. N.D. G1299T R433S 2࢒ Normal G1898A R633Q 2࢒ Normal G2012T G671V ࢒ Normal G2168A R723Q 2 Normal G2965A A989T 2࢒ Normal G3140C C1047S 1࢒ Normal G3173A R1058Q ࢒ Normal C4535T S1512L ࢒ Normal ABCC2 MRP2 C-24T N.D. N.D. G1058A R353H N.D. N.D. G1249A V417I ࢒ Normal C2366T S789F 12 Intracellular T2780G L927R N.D. N.D. C3298T R1100C N.D. N.D. G3299A R1100H N.D. N.D. T3563A V1188E N.D. N.D. G4348A A1450T ࢒ Normal/Intracellular G4544A C1515Y N.D. N.D. ABCC3 MRP3 G32A G11D ࢒ Normal C202T H68Y N.D. N.D. G296A R99Q N.D. Normal C1037T S346F 2 Normal C1537A Q513K N.D. N.D. T1643A L548Q N.D. N.D. G1820A S607N 2 Normal C2221T Gln741STOP N.D. N.D. G2293C V765L ࢒ Normal G2395A V799M N.D. N.D. C2758T P920S 1 Normal G2768A R923Q 1 Normal C3657A S1219R N.D. N.D. C3856G R1286G ࢒ Normal G3890A R1297H N.D. N.D. C4042T R1348C 1 Normal A4094G Q1365R ࢒ Normal C4141A R1381S ࢒ Intracellular C4217T T1406M N.D. N.D. G4267A G1423R N.D. N.D. ABCC4 MRP4 C52A L18I N.D. N.D. C232G P78A 2࢒ Normal T551C M184T N.D. N.D. G559T G187W 2 Reduced A877G K293E ࢒ Normal G912T K304N ࢒ Normal C1067T T356M N.D. N.D. C1208T P403L 2࢒ Normal G1460A G487E 2 Normal A1492G K498E ࢒ Normal A1875G I625M N.D. N.D. C2000T P667L N.D. N.D. A2230G M744V ࢒ Normal G2269A E757K N.D. Intracellular G2459T R820I N.D. N.D. G2560T V854F N.D. N.D. G2698T V900L N.D. N.D. G2867C C956S 1࢒ Normal G3211A V1071I ࢒ Normal C3425T T1142M N.D. N.D. G3659A R1220Q N.D. N.D. A3941G Q1314R N.D. N.D. 2, reduced function; 1, increased function; ࢒, no change in function; N.D. not determined. Login to comment

PMID: 15167703 [PubMed] Lang T et al: "Genetic polymorphisms in the multidrug resistance-associated protein 3 (ABCC3, MRP3) gene and relationship to its mRNA and protein expression in human liver."

No. Sentence Comment

5 SNPs 39G>C (allele frequency: 0.5%, located in exon 1), 202C>T (1.6%, exon 2), 1037C>T (0.5%, exon 9), 1537C>A (0.5%, exon 12), 3890G>A (5.2%, exon 27) and 4267G>A (0.6%, exon 29) resulted in Lys13Asn, His68Tyr, Ser346Phe, Gln513Lys, Arg1297His and Gly1423Arg amino acid substitutions, respectively. Login to comment
76 A; Gln513Lys; 0.5%), exon 27 (3890G.A; Arg1297His; 5.2%) and exon 29 (4267G.A; Gly1423Arg; 0.6%) resulted in amino acid substitutions (Fig. 1). Login to comment
100 Table 2 Polymorphisms identified in the MRP3 gene and frequencies of MRP3 mutations estimated among 103 Caucasian individuals Frequency (%) SNP ID 5` Sequence Genetic variation 3` Sequence Region Effect Alleles n Heterozygous Homozygous NCBI SNP ID 1 GAAGCCGGTG À1942G.T GTAGACAAGG Promoter 186 2.2, 0.4-6.6 (2.2) 0.0, 0.0-3.2 (0.0) 2 AGTCCCAGAG À1767G.A CATCAAGGAG Promoter 186 22.6, 15.7-30.9 (21.7) 1.1, 0.1-5.0 (1.5) rs1989983 3 GAGGTGGCTT À1328G.A CCCCTTCTGC Promoter 190 12.6, 7.5-19.7 (11.8) 0, 0.0-3.1 (0.4) 4 GGCTCCCACC À1298C.G ACACCTGCCG Promoter 192 2.1, 0.4-6.4 (2.1) 0, 0.0-3.1 (0.0) 5 TGAAACTGGA À1213C.G AGACCTGTGG Promoter 184 21.7, 14.9-30.0 (21.1) 1.1, 0.1-5.1 (1.4) 6 CCCCAACAAG À1134C.T GGTGCTGAGT Promoter 190 4.2, 1.5-9.4 (4.1) 0.0, 0.0-3.1 (0.0) rs4148403 7 ACCTGTCCTT À897delC CCCCCCCAAC Promoter 196 45.9, 37.3-54.7 (43.7) 9.2, 4.9-15.5 (10.3) rs4148404 8 CAGAGGGAAT À860T.G CACACATGTT Promoter 188 1.1, 0.1-4.9 (1.1) 0.0, 0.0-3.1 (0.0) 9 TCCCCCTGGC À260T.A TGGCCCAGGG Promoter 180 23.9, 16.8-32.4 (20.9) 1.1, 0.1-5.1 (1.6) 10 AGGGCCCCCC À211C.T ACCTCTGCCC Promoter 198 58.6, 49.8-67.0 (50.0) 21.2, 13.8-28.0 (24.5) rs4793665 11 TGGGTCCGAC À35C.A GCGCTCGCCT Exon 1 non-coding 196 1.0, 0.1-4.7 (1.0) 0.0, 0.0-3.0 (0.0) 12 TCGGCTCCAA 39G.C TTCTGGGTAA Exon 1 K13N 198 1.0, 0.1-4.7 (1.0) 0.0, 0.0-3.0 (0.0) 13 TTCTCTGTGT 46-6C.T CCCAGGACTC Intron 1 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 14 ACCTGTGGGT 141C.T GCCCTGCCCT Exon 2 silent 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 15 CATCCTCTCC 202C.T ACCTGTCCAA Exon 2 H68Y 192 3.1, 0.9-7.9 (3.1) 0.0, 0.0-3.1 (0.0) 16 CCAACCTGTG 223-12C.T TCTCTTCGCA Intron 2 202 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 17 GGGAAGAAGA 349-102A.C GGGGGTGGCC Intron 3 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 18 GGGGTGGCCC 349-90C.T AGAAACTTCT Intron 3 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 19 GAGAAATGGA 349-53G.A GCAGGTCCAG Intron 3 196 5.1, 2.0-10.4 (5.0) 0.0, 0.0-3.0 (0.1) rs2301836 20 CAGCCCCCAA 612þ73C.A CCCTCCAGTT Intron 5 166 10.8, 5.8-18.2 (10.2) 0.0, 0.0-3.5 (0.2) 21 TGATTCCCCC 613-22G.A TCCTATTCTC Intron 5 168 45.2, 36.0-54.8 (40.8) 6.0, 2.4-12.1 (8.2) rs739923 22 ACCCACTGCT 807-18C.T CTTCCTCCCT Intron 7 176 12.5, 7.2-19.8 (13.6) 1.1, 0.1-5.3 (0.6) rs2301837 23 TCCACACTCC 998þ16G.A GCTCACTATA Intron 8 154 7.8, 3.4-14.8 (7.5) 0.0, 0.0-3.8 (0.1) 24 ATGGCCCCCT 1037C.T CTGGTGGGGC Exon 9 S346F 202 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 25 TGCTTCCTGC 1339-107C.G CATCTACACA Intron 10 170 1.2, 0.1-5.5 (1.2) 0.0, 0.0-3.5 (0.0) 26 TGCCTCCTCA 1339-1G.T AACCTAGGTC Intron 10/Exon 11 splice site 174 1.1, 0.1-5.3 (1.1) 0.0, 0.0-3.4 (0.0) 27 TGAAGCTGTA 1512C.T GCCTGGGAGC Exon 12 silent 204 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 28 CTTCCTGAAG 1537C.A AGGTGGAGGG Exon 12 Q513K 204 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 29 GGAGGGCATC 1552A.C GGCAGGGTGA Exon 12 silent 202 6.9, 3.3-12.6 (6.7) 0.0, 0.0-2.9 (0.1) 30 CTTCCTGGTG 1635þ4delA GGCTTGGCAC Intron 12 splice site consenus 204 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 31 TGCTGGACGC 1695C.T GAGAAGGCCT Exon 13 silent 204 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 32 GTCCTCCTTT 1871-79C.T CCCTGCCCCC Intron 14 202 23.8, 17.0-31.8 (22.5) 75.2, 67.2-82.2 (75.8) rs879459 33 TTCCCTGCCC 1871-70C.G CCAGCCTCCC Intron 14 202 1.0, 0.1-4.6 (1.0) 0.0, 0.0-2.9 (0.0) 34 CTCCCTGACC 1871-22C.G TGCCCACCTT Intron 14 202 2.0, 0.4-6.1 (2.0) 0.0, 0.0-2.9 (0.0) 35 ACCTGCCCCC 1926C.A ACTCTGCACA Exon 15 silent 202 3.0, 0.8-7.5 (3.0) 0.0, 0.0-2.9 (0.0) 36 AGATTGGAGA 2238G.A AAGGTACAGA Exon 17 silent 166 1.2, 0.1-5.6 (1.2) 0.0, 0.0-3.5 (0.0) 37 AAGAGGCTAG 2241þ34G.C GCATAGAGCT Intron 17 166 41.0, 31.8-50.6 (42,0) 49.4, 39.9-58.9 (48.8) 38 TTCACACATT 2241þ97G.A GTGTAACGTT Intron 17 160 6.3, 2.5-12.7 (6.7) 1.3, 0.1-5.8 (0.3) 39 CCTTTCAATC 2600-123C.T CCCTCATTTT Intron 19 196 55.1, 46.3-63.7 (47.4) 11.2, 6.4-17.9 (15.0) rs4148415 40 CCAGCCCTCC 2714þ29C.T GGAGGCTGTA Intron 20 196 52.0, 43.3-60.7 (46.7) 11.2, 6.4-17.9 (13.9) rs2072365 41 GGCCTCCCCA 2714þ53A.G GCCCTGCCAG Intron 20 196 46.9, 38.3-55.7 (43.3) 8.2, 4.1-14.2 (10.0) rs2072366 42 TGAGGCTGGG 3039C.T GTCTATGCTG Exon 22 silent 156 10.3, 5.2-17.7 (12.1) 1.3, 0.1-5.9 (0.4) rs4148416 43 CCCCCCAAAC 3067þ71C.T GTGCCCTTGC Intron 22 180 20.0, 13.3-28.2 (19.8) 1.1, 0.1-5.2 (1.2) 44 TTATTGGGGC 3378þ47G.A GGGCAACACA Intron 23 202 11.9, 7.0-18.5 (11.2) 0.0, 0.0-2.9 (0.4) 45 ACACATGGGC 3378þ63G.T GGGGCAGCAG Intron 23 202 3.0, 0.8-7.5 (3.0) 0.0, 0.0-2.9 (0.0) 46 TCCCTCCTTT 3579-66C.T CCCTAAGCAG Intron 24 196 10.2, 5.6-16.7 (9.7) 0.0, 0.0-3.0 (0.3) rs967935 47 TATTCTGTGC 3890G.A CTACCGGCCG Exon 27 R1297H 192 10.4, 5.8-17.0 (9.9) 0.0, 0.0-3.1 (0.3) 48 TGCATGTGCA 3942C.T GGTGGCGAGA Exon 27 silent 192 30.2, 22.5-38.8 (31.1) 4.2, 1.4-9.3 (3.8) rs2277624 49 AGGTACGCGT 3954þ9G.T GGGTAGGCGG Intron 27 192 1.0, 0.1-4.8 (1.0) 0.0, 0.0-3.1 (0.0) 50 CTCAGAGGGC 4267G.A GGGAGAATCT Exon 29 G1423R 180 1.1, 0.1-5.2 (1.1) 0.0, 0.0-3.3 (0.0) 51 TAGTAGCTGA 4509A.G TTTGATTCTC Exon 31 silent 176 22.7, 15.6-31.3 (21.9) 1.1, 0.1-5.3 (1.6) rs1051640 SNPs with the ID 6, 7, 19, 21, 22, 32, 39, 40, 41, 42, 46, 48 and 51 previously reported by Saito et al. [13]. Login to comment
104 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 1 16 75 117 163 205 226 269 333 393 447 478 595 624 646 689 748 804 867 905 954 1023 1127 1199 1236 1270 1319 1372 1427 1493546 K13N H68Y S346F Q513K R1297H G1423R splice site mutation SNPs: P Exon: H2N out membrane in TMDs ATP TMDs ATP COOH Fig. 1 MRP3 gene and predicted two-dimensional protein structure using the MRP3 protein topology of Swiss-Prot O15438. Login to comment