ABCMdb

ABCG2 p.Pro269Ser

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Publications

PMID: 15553238 [PubMed] Kondo C et al: "Functional analysis of SNPs variants of BCRP/ABCG2."

No. Sentence Comment

3 The cellular localization was identified using the wild type and seven different SNP variants of BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N BCRP) after transfection of their cDNAs in plasmid vector to LLC-PK1 cells. Login to comment
8 Furthermore, the transport activity of E1S, DHEAS, MTX, and PAH normalized by the expression level of BCRP protein was almost the same for the wild type, V12M, Q141K, A149P, R163K, Q166E, and P269S BCRP. Login to comment
27 The allele frequencies of these SNPs are 18, 1, 36, 1, 0.5, 0.5, and 0.5%, respectively. In the 84 cell lines, 7 kinds of SNPs were identified and their frequency for G34A (V12M), C376T (Q126Stop), C421A (Q141K), G445C (A149P), G488A (R163K), C805T (P269S), and G1098A (E366E) are 22, 3, 29, 1, 0.6, 0.6 and 2%, respectively. Login to comment
29 We constructed expression systems for the wild type and SNPs variants of BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, S441N BCRP) and examined whether these SNPs variants of BCRP alter its localization, expression level, and transport activity. Login to comment
42 Using site-directed mutagenesis, SNP variants of BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S and S441N BCRP) were constructed on pcDNA3.1 vector (SNPs type BCRP/pcDNA3.1). Login to comment
48 P269S BCRP was amplified with 5Ј-GACTTATGTTCCACGGGTCTGCT- CAGGAGGCCTTGGG-3Ј and 5Ј-CCCAAGGCCTCCT- GAGCAGACCCGTGGAACATAAGTC-3Ј. Login to comment
52 For SNPs type BCRPs, viruses were prepared in the same way, resulting in the production of pAd-SNPs BCRP (pAd-V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N BCRP). Login to comment
110 Except for two SNP variants of BCRP (Q141K and S441N BCRP), the ATP-dependent uptakes per mg membrane protein of SNP variants (V12M, A149P, R163K, Q166E, P269S BCRP) were similar to that of the wild-type BCRP (Fig. 3a). Login to comment
114 As shown in Fig. 3b, the transport activity of other SNP variants of BCRP (V12M, Q141K, A149P, R163K, Q166E, and P269S BCRP) was almost identical to that of the wild-type BCRP. Login to comment
120 Figure 5a shows the ATP-dependent uptake of DHEAS, PAH, and MTX per mg membrane protein for the wild-type and SNPs BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N BCRP). Login to comment
162 For these compounds, our results indicated that the transport activity per BCRP molecule for 6 kinds of SNP variants (V12M, A149P, R163K, Q166E, P269S, and also Q141K BCRP) is almost the same as that of the wild type BCRP (Figs. Login to comment

PMID: 15598215 [PubMed] Wang H et al: "Linkage disequilibrium and haplotype architecture for two ABC transporter genes (ABCC1 and ABCG2) in Chinese population: implications for pharmacogenomic association studies."

No. Sentence Comment

57 SNP Nucleotide sequence Minor allele dbSNP ID effect position (major/minor) frequency (%) ABCC1 1 5`FR/-1862 gacccG/Aggcca 44.4 2 5`FR/-1830 atcctA/Gtctac 1.9 3 5`FR/-1680 gaggaG/Aaaaag 1.9 4 5`FR/-471 cggatA/Gctgtc 7.4 5 E2/218 caaaaC/Tcaaaa 3.7 Thr73Ile 6 I2/-26 gttgtG/Aggggg 1.9 rs8187842 7 I3/-66 ctgggT/Cgacaa 37.0 rs4148337 8 I7/+54 ccactC/Actgtg 9.3 rs903880 9 I7/+64 ggcctC/Gaatcc 48.1 rs246232 10 E8/816 cagccG/Agtgaa 1.9 wobble 11 E8/825 aaggtT/Cgtgta 38.9 rs246221 wobble 12 E9/1062 gtgaaT/Cgacac 35.2 rs35587 wobble 13 I9/+8 aggggA/Gcgctg 37.0 rs35588 14 I12/-37 cactcA/Ggggca 20.4 rs35604 15 E13/1684 tggccT/Ctgtgc 20.4 rs35605 wobble 16 I13/+105 ccggtC/Tgggct 20.4 rs35606 17 I14/+105 ccagcC/Tgcttg 1.9 18 I15/+627 gctgtA/Gtttta 25.8 rs35628 19 I15/+669 aatctG/Ttagaa 7.4* rs4148353 20 I15/-967 ctttcT/Ggctgt 37.0 rs152029 21 E16/2007 atcccC/Tgaagg 3.7 rs2301666 wobble 22 E17/2168 tctccG/Aagaaa 5.6 rs4148356 Arg723Gln 23 I18/-30 gcactG/Cacgtg 16.7 rs2074087 24 I22/+62 aattaT/Ctccct 27.8 rs3887893 25 I22/-43 gtcagC/Ttccct 3.7 26 E27/3915 gaggaC/Tctgga 1.9 wobble 27 E28/4002 aagtcG/Atccct 11.1 rs2239330 wobble 28 I28/-35 tcagcA/Gtgaca 27.8 rs212087 29 I30/+30 gcacaG/Atggcc 29.6 rs212088 30 3`UTR/+801 accccC/Gactcc 33.3 rs129081 noncoding 31 3`UTR/+866 tactgT/Atccca 14.8 rs212090 noncoding 32 3`FR/+1513 gttctT/Ctaagg 27.8 ABCG2 1 5`UTR/-407 cgcagC/Tgcctc 1.9 2 5`UTR/-376 ggggaG/Acgctc 1.9 3 E2/34 tcccaG/Atgtca 20.4 rs2231137 Val12Met 4 I2/+36 ttttaA/Gtttac 25.9 rs4148152 5 I3/+10 gtataA/Ggagag 20.4 rs2231138 6 E5/421 acttaC/Agttct 22.2 rs2231142 Gln141Lys 7 E7/805 acgggC/Tctgct 3.7 Pro269Ser 8 I9/-126 agccaT/Gtgagt 7.4 9 I11/+20 gttctA/Gggaac 31.5 rs2231153 10 I12/+49 cctatG/Tggtga 16.7 rs2231156 11 I13/+40 tgtttT/Ctttcc 24.1 rs2231157 12 I13/-21 tgactC/Tttagt 29.6 rs2231162 13 I14/-46 ttcttG/Aaaatt 48.1 rs2725267 SNPs in specific regions, i.e. 5`flanking region (5`FR), 5`untranslated region (5`UTR), intron (I), exon (E), 3`UTR, and 3`FR, are presented as region/+(-): for 5`FR and 5`UTR, n nucleotides upstream (-) from the translation initiation site; for 3`UTR and 3`FR, n nt downstream (+) from the third base of stop codon; for coding regions, n corresponds to positions of their cDNA with the first base of start codon set to 1; and for introns, n nt upstream (-) from 3` site or downstream (+) from 5` site of introns. Login to comment

PMID: 15743976 [PubMed] Vethanayagam RR et al: "Functional analysis of the human variants of breast cancer resistance protein: I206L, N590Y, and D620N."

No. Sentence Comment

220 Several other BCRP variants occurring at much lower allele frequencies (0.5-1%) such as A149P, R163K, Q166E, P269S, and S441N have also been characterized (Kondo et al., 2004). Login to comment

PMID: 16337740 [PubMed] Cervenak J et al: "The role of the human ABCG2 multidrug transporter and its variants in cancer therapy and toxicology."

No. Sentence Comment

94 In addition to the aa 482 ABCG2 mutations, several other variants [c.445GOC (A149P), c.458COT (T153M), c.488GOA (R163K), c.805COT (P269S)] leading to coding sequence changes were identified in different cell lines that were also not detected in healthy individuals [47,55]. Login to comment
147 In a recent study, similarly LLC-PKI cells where used to express the V12M and Q141K variants and additionally five other polymorphisms (A149P, R163K, Q166E, P269S and S441N [55]). Login to comment

PMID: 16702730 [PubMed] Maekawa K et al: "Genetic variation and haplotype structure of the ABC transporter gene ABCG2 in a Japanese population."

No. Sentence Comment

89 On the other hand, several nonsynonymous SNPs reported in other ethnic groups were not detected: 805CÀT (Pro269Ser) found in Chinese at a 0.037 frequency,20) 1858GÀA (Asp620Asn) in undened (combined) ethnicities14) (0.011) and in a Dutch population21) (0.005), 616AÀC (Ile206Leu) in Hispanics (0.100), and 1768AÀT (Asn590Tyr) in Caucasians (0.010).18) Thus, these SNPs are either ethnic-specic or rare. Login to comment

PMID: 17015488 [PubMed] Sarkadi B et al: "Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system."

No. Sentence Comment

824 It is worth noting that in addition to the amino acid 482 ABCG2 mutations, several other variants, A149P, T153M, R163K, and P269S, were identified in different cell lines that were also not detected in healthy individuals (188, 247) (Fig. 11). Login to comment

PMID: 17228519 [PubMed] Tamura A et al: "Genetic polymorphisms of human ABC transporter ABCG2: development of the standard method for functional validation of SNPs by using the Flp recombinase system."

No. Sentence Comment

142 Finally, the acquired mutants R482G and R482T form another group, which is characteristic Standard method for functional validation of ABCG2 SNPs Journal of Experimental Therapeutics and Oncology Vol. 6 2006 9 Table 3 Remarks mRNA Protein Author Ref Host cell Vector Expression SNP expression expression Imai et al. (15) PA317 pHaL-IRES-DHFR bicistronic Stable V12M Similar to WT Similar to WT - - retrovirus vector plasmid - Q141K Similar to WT Lower than WT Mizuarai et al. (18) LLC-PK1 pcDNA3.1(+) Stable V12M Similar to WT N.D. - - - - Q141K Similar to WT N.D. Morisaki et al. (25) HEK293 pcDNA3.1 Stable V12M Vary among clones Vary among clones - - - - Q141K Vary among clones Vary among clones - - - - D620N Vary among clones Vary among clones Kondo et al. (26) LLC-PK1/ pcDNA3.1/ Stable/ V12M N.D. Similar to WT - HEK293 Adenovirus Transient Q141K N.D. 30 - 40% of WT - - - - A149P N.D. Similar to WT - - - - R163K N.D. Similar to WT - - - - Q166E N.D. Similar to WT - - - - P269S N.D. Similar to WT - - - - S441N N.D. Lower than WT Vethanayagam (27) HEK293 pcDNA3.1/myc-His(-) Stable I206L N.D. Vary among clones et al. - - - - N590Y N.D. Vary among clones - - - - D620N N.D. Vary among clones N.D.: No data Table 2. Login to comment

PMID: 17237154 [PubMed] Lee SS et al: "Identification and functional assessment of BCRP polymorphisms in a Korean population."

No. Sentence Comment

3 BCRP V12M, Q141K, P269S, and Q126Stop were detected at frequencies of 23, 28, 0.2, and 1.9%, respectively. These four coding variants were also screened in Chinese and Vietnamese subjects; the allelic frequencies among the three populations were compared; and predictions were made as to the potential frequency of each variant. Login to comment
4 In vitro functional analyses of the P269S protein and the promoter SNP -19031C>T (mutated in the hypoxia-inducible factor-1␣ binding site) were performed and compared with those of the wild type. Login to comment
5 P269S exhibited a 35 to 40% decrease in vesicular uptake of [3 H]estrone-3-sulfate and [3 H]methotrexate compared with the wild type. Login to comment
7 Our results suggest that the P269S variant could be a functionally altered variant. Login to comment
33 Therefore, we investigated, for the first time, genetic polymorphisms of the BCRP gene in a Korean population and performed in vitro functional characterization of a novel regulatory SNP and a coding SNP (P269S). Login to comment
34 The functional capability of the P269S variant to take up [3 H]estrone-3-sulfate (ES) and [3 H]MTX has been reported as being comparable with that of the wild-type protein TABLE 1 Primer sequences used for the amplification of the BCRP gene fragment and the annealing temperatures used in the PCR Name Region Primer Sequence (5Ј33Ј) Size PCR Condition base pair Tm; °C BCRP1P Promoter F: AACCCAGCTAGGTCAGACGA 557 60.0 R: TTTGAGTGGGCACAGCAC BCRP2P Promoter F: TTCCTAGGGTAGATGCAGCAG 509 60.0 R: CAGGGACAAGCCAAACACTC BCRP3P Promoter F: GTAGAGGCAGGGTTTCACCA 559 60.0 R: AAGTGATTGCGCATGTTCAG BCRP4P Promoter F: CGTGCCTGGCCTCTATGTAT 572 60.0 R: CTGACGCAGGCAGATCACT BCRP5P Promoter F: GCCACCACACCCAGTGTAAT 518 64.7 R: TGCAAAGTAAAAACAAATCAAAACC BCRP1E Exon 1 F: AGCTCGTCCCCTGGATGT 516 54.0 R: CCACCAACCTTTCCAGACAC BCRP2E Exon 2 F: CTGCTCATTGCCACACATTT 400 54.0 R: GCCAAAACCTGTGAGGTTCA BCRP3E Exon 3 F: GTCTCAAACTCCTGGCCTCA 403 54.0 R: GCGTTGCAAATGCTCAATAA BCRP4E Exon 4 F: TGGATTCAAAGTAGCCATGAGA 402 54.0 R: ATTCTCCCTGCCTTTTCACA BCRP5E Exon 5 F: GGTTCATCATTAGCTAGAACTTTACC 403 54.0 R: TGGAAAGCAACCATTTTTGA BCRP6E Exon 6 F: TCTTACAGGACTGGCACACG 426 54.0 R: CCTTCCCTACATTCTTACCTGCT BCRP7E Exon 7 F: TCAGGCTGAACTAGAGCAAACA 387 60.0 R: AGCACCAAATGGAACAAACA BCRP8E Exon 8 F: CATGGGAAGAAGAGAGAAAGAAA 412 60.0 R: CAAAAACACCAACAGCACTCA BCRP9E Exon 9 F: GGTGTTAGGGAAGCATCCAA 413 54.0 R: TGAAGCAGATGATAACAGAACCA BCRP10E Exon 10 F: GCCAAGCCATTGAGTGTTTA 386 60.0 R: TGGGCAACAGAGCATGAC BCRP11E Exon 11 F: CCACAACAATCCAAGACTGTG 423 60.0 R: GTAATCCTCCGGATCCCATC BCRP12E Exon 12 F: GGTCTAGCCCTGAGGATGTG 403 64.7 R: GAGTGCAAAATGGACAGGTG BCRP13E Exon 13 F: AGGGTGGTTGGAGAGTGGAT 412 60.0 R: AGCAGAGCCCCATTTACAGA BCRP14E Exon 14 F: TGAGTGTCTTGAGTAAGTGGAGAGA 420 54.0 R: GACTCCCCAGCCTTGTGTTA BCRP15E Exon 15 F: TCTTGATTGCCAGGGAAAAT 404 60.0 R: CGCGCACAACTCACTTTATG BCRP16E Exon 16 F: TGACGGATGCTAGGAATGAA 430 64.7 R: CCCATGGTTACTGTCTGAGGA TABLE 2 Primer sequences used for the pyrosequencing-based genotyping of functional BCRP variants SNPa Variant Primer Sequence (5Ј33Ј) Size PCR Condition base pair Tm; °C 34GϾA V12M 5Ј-Biotin-CTCTCCAGATGTCTTCCAGTAATG-3Ј 278 54.0 5Ј-GCCAAAACCTGTGAGGTTCA-3Ј For sequencing: 5Ј-AGTGTTCCTTTGTGGTTAC-3Ј 8191CϾT Q126Stop 5Ј-Biotin-ACTATCAGCCAAAGCACTTACCC-3Ј 174 54.5 5Ј-GTCTTAGCTGCAAGGAAAGATCCA-3Ј For sequencing: 5Ј-AATGTAATTCAGGTTACGTG-3Ј 8825CϾA Q141K 5Ј-Biotin-GTTGCAAGCCGAAGAGCTG-3Ј 69 54.0 5Ј-TGATGTTGTGATGGGCACTC-3Ј For sequencing: 5Ј-GACGGTGAGAGAAAACTT-3Ј 21850CϾT P269S 5Ј-Biotin-TAGCACCAAATGGAACAAACAC-3Ј 236 54.0 5Ј- TGTTTGATAGCCTCACCTTATTGG-3Ј For sequencing: 5Ј-GAAGACTTATGTTCCACG-3Ј a Position is indicated with respect to the start codon (ATG) of the BCRP gene; the A in the ATG triplet is designated as ϩ1, and the next base toward the 5Ј-end is designated as -1. Login to comment
36 However, in the present study, BCRP P269S from human blood samples (not from cell lines) was used for the first time. Login to comment
37 Functional information on P269S is sparse, as compared with the amount of information that has been collected for other coding variants, such as V12M, Q141K, and the null allele Q126Stop. Login to comment
38 Because proline is known to be a helix breaker, the three-dimensional structure of the BCRP protein may be affected in the P269S variant. Login to comment
39 Therefore, we performed a functional study of the P269S variant among the four variants identified in the study (V12M, Q141K, P269S, and Q126Stop). Login to comment
65 All the subjects were screened for BCRP V12M, Q126Stop, Q141K, and P269S. Login to comment
83 The BCRP R482-P269S and G482-P269S variants were generated by an overlap extension procedure using specific primers that introduced amino acid substitutions: 5Ј-AGGCCTCCT- GAGCAGACCCGTGGAACATAAG-3Ј and 5Ј-CTTATGTTCCACGGGTC- TGCTCAGGAGGCCT-3Ј. Login to comment
105 SNP and Positionb Position Relative to Transcription Start Site Location Effect N Allelic Frequency % 1 -20296AϾG -1379 Promoter 92 13 2 -19855CϾT -938 Promoter 92 0.5 3 -19605AϾG -688 Promoter 92 0.5 4 -19031CϾT -114 Promoter 92 1.6 5 -18631CϾT ϩ286 5ЈUTR 92 2.2 6 34GϾA Exon 2 V12M 275 23 7 238AϾG Intron 2 92 25 8 7430AϾG Intron 3 92 9.8 9 8191CϾT Exon 4 Q126Stop 375 1.9 10 8825CϾA Exon 5 Q141K 275 28 11 21850CϾT Exon 7 P269S 674 0.2 12 26297GϾA Exon 9 92 1.1 13 38485AϾG Intron 11 92 24 14 40086insA Intron 12 92 0.5 15 40110GϾT Intron 12 92 22 16 42288CϾT Intron 13 92 67.4 17 42313TϾG Intron 13 92 2.2 18 44072CϾT Intron 13 92 23.4 19 44997AϾG Intron 14 92 49.5 20 45235CϾT Intron 15 92 20.1 a The reference sequence used has GenBank accession no. Login to comment
149 The four coding SNP were 34GϾA coding for V12M, 8191CϾT coding for Q126Stop, 8825CϾA coding for Q141K, and 21850CϾT coding for P269S. Login to comment
150 For more extensive evaluation of the allelic frequencies of the four BCRP variants found in the Korean population, the remaining 183 subjects were screened by pyrosequencing for the presence of V12M, Q126Stop, Q141K, and P269S. Login to comment
153 Q126Stop and P269S were found in 1.9 and 0.2% of Koreans, respectively. Login to comment
155 Recently, Kondo et al. (2004) reported the identification of several BCRP variants, which include A149P, R163K, Q166E, P269S, and S441N, in human cell lines. Login to comment
156 With the exception of the BCRP P269S variant, these variants were not observed in this study. Login to comment
163 The BCRP haplotypes for 11 common SNP with frequencies Ͼ5% were analyzed )A( WT P269S Mock 0 05 001 051 002 052 003 053 [3 H]MTXuptake(pmol/min/mgprotein) TW S962P * [3 H]ESuptake(pmol/min/mgprotein) )B( )C( 0 52 05 57 001 521 TW S962P * FIG. 3. Login to comment
164 In vitro functional characterization of the BCRP P269S variant. Login to comment
165 A, vesicular uptake of [3 H]MTX in membranes obtained from Sf9 cells that express the wild-type BCRP protein or the BCRP P269S variant protein. Login to comment
167 BCRP P269S exhibited significantly decreased activity compared with the wild type in a two-tailed Student`s t test; ‫,ء‬ p Ͻ 0.05. Login to comment
168 B, vesicular uptake of [3 H]ES membranes obtained from Sf9 cells that express the wild-type BCRP protein or the BCRP P269S variant protein. Login to comment
190 Transporter Activity of the P269S Variant. Login to comment
191 Two different comparisons of the wild-type and P269S variant proteins were performed. Login to comment
192 Vesicular uptake of [3 H]MTX and [3 H]ES into the microsomal fraction was measured for the BCRP wild-type and P269S proteins expressed in Sf9 cells. Login to comment
193 BCRP P269S-expressing microsomes showed about 35 to 40% decrease in [3 H]MTX and [3 H]ES uptake compared with microsomes that expressed the wild-type BCRP (Fig. 3, A and B). Login to comment
194 The expression levels of the wild-type and P269S BCRP proteins were similar, as confirmed by immunoblotting (Fig. 3C). Login to comment
195 To investigate whether the decreased functionality of BCRP P269S was derived from the modulation of substrate-dependent ATPase activity, prazosin-induced ATPase activity was measured in the wild-type and P269S-expressing microsomes from Sf9 cells. Login to comment
197 The BCRP ATPase activity in the presence of prazosin of the P269S variant was also the same as that of the wild-type protein, which indicates that the decreased activity of P269S is not related to ATPase activity. Login to comment
200 From the screening of four nonsynonymous variants in other ethnic groups, the allelic frequencies of V12M, Q126Stop, Q141K, and P269S were obtained (Table 4). Login to comment
203 The P269S variant was not observed in 100 Caucasians and 100 African-Americans, which suggests that this variant is a rare variant that is found only in Asians. Login to comment
209 Prazosin-dependent ATPase activity of the BCRP P269S variant. Login to comment
210 A, ATPase activities of Sf9 cells that express the wild-type BCRP protein or the BCRP P269S variant protein. Login to comment
223 P269S was observed exclusively in Koreans and Vietnamese and not in the Caucasian, African-American, and Chinese populations. Login to comment
234 Our results on BCRP haplotypes in the Korean population TABLE 4 Haplotype distribution of BCRP gene in Koreans PNS 69202- G>A 43 A>G 832 G>A 0347 G>A 5288 A>C 58483 G>A 01104 T>G 88224 T>C 27044 T>C 79944 G>A 53254 T>C ycneuqerF )%( egnahcAA K141QM21V 4.621 2 9.91 3 8.7 4 6.7 5 4.7 6 9.5 7 7.4 8 9.2 9 5.2 01 8.1 11 7.1 21 4.1 31 1.1 Haplotype 41 1.1 TABLE 5 Expected allelic frequencies of BCRP V12M, Q126Stop, Q141K, and P269S variants in different Asian populations Population No. Login to comment
235 of Subjects Allelic Frequency (95% CI) V12M Q126Stop Q141K P269S % % % % Korean 275-674a 23 (19.6-26.6) 1.9 (0.9-2.9) 28 (23.8-31.2) 0.2 (0-0.4) Chinese 191 33b (28.5-37.9) 0.5 (0-1.2) 29 (24.3-33.3) 0 (0-0.1) Vietnamese 140 36b (30.8-42.0) 0.4 (0-1.1) 31 (25.7-36.5) 0.7 (0-1.7) a The numbers of subjects genotyped for the V12M, Q126Stop, Q141K, and P269S variants were 275, 375, 275, and 674, respectively. Login to comment
250 In the present study, we have described the allele frequencies for BCRP variants in a Korean population and analyzed the function of the P269S coding variant. Login to comment
251 Kondo et al. (2004) have reported that the P269S variant has activity similar to that of the wild-type protein. Login to comment
252 However, in at least three repeated experiments, we showed that P269S shows altered ES and MTX uptake as compared with the wild type. Login to comment
253 Both the previous study and our current study show similar protein levels of P269S variant and wild-type protein expression in the systems used. Login to comment
257 Therefore, the possibility that P269S variation may not change the BCRP activity in mammalian cells cannot be ruled out. Login to comment

PMID: 17504223 [PubMed] Xia CQ et al: "Evaluation of drug-transporter interactions using in vitro and in vivo models."

No. Sentence Comment

119 The function of seven single nucleotide polymorphisms (SNPs) in BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N BCRP) was determined using membrane vesicles from HEK293 cells infected with the recombinant adenoviruses containing the corresponding BCRP cDNAs [45]. Login to comment
121 Furthermore, the transport rate of estrone sulfate, dehydroepiandrosterone sulfate (DHEAS), methotrexate, and p-aminohippurate was almost the same for the wild type, V12M, Q141K, A149P, R163K, Q166E, and P269S BCRP variants when it is normalized by the expression levels of BCRP protein. Login to comment

PMID: 18363541 [PubMed] Tamura A et al: "Drug-induced phototoxicity evoked by inhibition of human ABC transporter ABCG2: development of in vitro high-speed screening systems."

No. Sentence Comment

230 Plasma membrane Outside Inside ATP-binding cassette H2 N COOH V12M G51C Q126stop Q141K T153M R160Q Q166E I206L F208S S248P E334stop F431L F489L S441N R482G R482T F571I R575stop N590Y D620N T542A A528T D296H P269S A. Login to comment

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

No. Sentence Comment

250 It should be noted that many xeno- and endobiotic BCRP Figure 5 Predicted membrance topology of BCRP (ABCG2) based on hydrophobicity analysis. Locations of the non-synonymous polymorphisms are indicated with arrows. See Table 5 for allele frequencies and description of funtional consequences. NH2 COOH NBD Val12Met Gly51Cys Gln126* Ala149Pro Gln141Lys Thr153Met Arg160Gln Arg163Lys Gln166Glu Phe506Ser Phe507Leu Val508Leu Met509* Phe489Leu Ser441Asn Phe431Leu Glu334* Ile206Leu Ala315del Thr316del Phe208Ser Asp296His Ser248Pro Pro269Ser Phe571Ile Arg575* Asn590Tyr Asp620Asn in out Membrane BCRP (ABCG2) NBD Val12Met NBDNBD Val12Met substrates are also transported by other efflux transporters, especially P-glycoprotein, thus extrapolating BCRP related in vitro data to the in vivo situation may be difficult. Login to comment

PMID: 18855611 [PubMed] Zhou SF et al: "Clinical pharmacogenetics and potential application in personalized medicine."

No. Sentence Comment

636 The localization of other variants including V12M, A149P, R163K, Q166E, P269S and S441N was also examined. Login to comment

PMID: 19200005 [PubMed] Porcelli L et al: "Intracellular trafficking of MDR transporters and relevance of SNPs."

No. Sentence Comment

201 Along with the above mentioned G34A, C421A and G1322A ABCG2 variants, the authors also studied the G445C (A149P), G488A (R163K), C496G (Q166E) and C805T (P269S) polymorphisms. Login to comment
204 [106] also reported similar protein levels of P269S variant and wild-type ABCG2. Login to comment
205 However, they showed that membrane vesicles obtained from Sf9 cells expressing the P269S variant displayed about 35 to 40% decrease in [3 H]methotrexate and [3 H]estrone-3-sulfate uptake compared with the ones expressing wild-type ABCG2, suggesting a decreased functionality of ABCG2 P269S. Login to comment

PMID: 19949928 [PubMed] Ross DD et al: "Impact of breast cancer resistance protein on cancer treatment outcomes."

No. Sentence Comment

90 found four nonsynonymous coding region SNPs among 92 Korean subjects (V12M, Q141K, P269S, Q126Stop), and four SNPs in the BCRP promoter region, one of which was in the HIF-1 response element (C-19031T) (86). Login to comment

PMID: 21103975 [PubMed] Meyer zu Schwabedissen HE et al: "In vitro and in vivo evidence for the importance of breast cancer resistance protein transporters (BCRP/MXR/ABCP/ABCG2)."

No. Sentence Comment

257 No effect on the in vitro transport activity was seen for the missense mutations c.445G>C (p.A149P; AF 0.01), c.458C>T (p.T153M; AF 0.033) c.496C>G (p.Q166E, AF not determined) c.616A>C (I206L AF not determined), c.488G>A (p.R163K AF 0.006), c.805C>T (p.P269S AF 0.006), and c.1711T>A (p.F571L, AF 0.005) (Kondo et al. 2004; Tamura et al. 2006). Login to comment

PMID: 21188243 [PubMed] Ishikawa T et al: "Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis."

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177 Gefitinib and imatinib are new anticancer drugs Outside Plasma membrane Inside H2N COOH V12M G51C Q126stop Q141K T153M R160Q Q166E I206L F208S S248P E334stop F431L F489L S441N R482G R482T F571I R575stop N590Y D620N T542A A528T D296H P269S ATP-binding cassette (a) 0 0.1 0.3 0.4 0.2 0.5 Mock WT V12M G51C Q126stop Q141K T153M Q166E I206L F208S S248P E334stop F431L S441N F489L F571I N590Y D620N R482G R482T ATP-dependenthematoporphyrin transport(nmol/min/mgprotein) (b) Figure 4: (a) Schematic illustration of human ABCG2 and its nonsynonymous polymorphisms. Login to comment

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

No. Sentence Comment

6589 Absent C421A Q141K 2 Normal/reduced G445C A149P ↔ Normal G448A R163K ↔ Normal C496G Q166E ↔ Normal/reduced A616C I206L 2↔ Normal T623C F208S N.D. Reduced T742C S248P N.D. Normal C805T P269S 2↔ Normal T1291C F431L 2 Normal/reduced G1322A S441N 2 Reduced T1465C F489L 2↔ Normal/reduced A1768T N590Y 2↔ Increased G1858A D620N 2↔ Normal 2, reduced function; ↔, no change in function; N.D. not determined. Login to comment

PMID: 16180115 [PubMed] Ito K et al: "Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport."

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212 Kondo et al. (119) also examined the cellular localization of a total of seven SNP variants of BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N) in LLC-PK1. Login to comment

PMID: 20799350 [PubMed] Kelly L et al: "Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains."

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72 Predictions of the Functional Effects of 40 nsSNPs in ABC Transporters Comon name HUGO name Mutation NBD Prediction BSEP ABCB11 E592Q NBD1 Neutral BSEP ABCB11 N591S NBD1 Neutral BSEP ABCB11 Q558H NBD1 Neutral BSEP ABCB11 V444A NBD1 Neutral BSEP ABCB11 E1186K NBD2 Disease MDR1 ABCB1 P1051A NBD2 Neutral MDR1 ABCB1 S1141T NBD2 Neutral MDR1 ABCB1 T1256K NBD2 Disease MDR1 ABCB1 V1251I NBD2 Neutral MDR1 ABCB1 W1108R NBD2 Disease MRP2 ABCC2 I670T NBD1 Disease MRP2 ABCC2 L849R NBD1 Disease MRP2 ABCC2 C1515Y NBD2 Disease MRP3 ABCC3 D770N NBD1 Neutral MRP3 ABCC3 K718M NBD1 Neutral MRP3 ABCC3 T809M NBD1 Disease MRP3 ABCC3 V765L NBD1 Disease MRP3 ABCC3 Q1365R NBD2 Disease MRP3 ABCC3 R1297H NBD2 Disease MRP3 ABCC3 R1348C NBD2 Disease MRP3 ABCC3 R1381S NBD2 Disease MRP4 ABCC4 G487E NBD1 Disease MRP4 ABCC4 K498E NBD1 Neutral MRP4 ABCC4 R1220Q NBD2 Neutral MRP4 ABCC4 T1142M NBD2 Neutral MRP4 ABCC4 V1071I NBD2 Neutral MRP6 ABCC6 I1330L NBD1 Neutral MRP6 ABCC6 I742V NBD1 Neutral MRP6 ABCC6 P664S NBD1 Neutral MRP6 ABCC6 R724K NBD1 Neutral MRP6 ABCC6 R769K NBD1 Neutral MRP6 ABCC6 A1291T NBD2 Neutral MRP6 ABCC6 E1369K NBD2 Neutral MRP6 ABCC6 G1327E NBD2 Disease MRP6 ABCC6 L1416R NBD2 Disease MRP6 ABCC6 R1268Q NBD2 Disease MRP6 ABCC6 R1461H NBD2 Disease MXR ABCG2 I206L NBD1 Neutral MXR ABCG2 P269S NBD1 Disease MXR ABCG2 Q141K NBD1 Neutral nsSNPs. Login to comment

PMID: 22869929 [PubMed] Huang L et al: "Deletion of abcg2 has differential effects on excretion and pharmacokinetics of probe substrates in rats."

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24 Several additional SNPs, including V12M, Q126Stop, and P269S, affect expression or activities of the transporter, which may also have clinical implications (Kondo et al., 2004; Mizuarai et al., 2004; Tamura et al., 2006; Lee et al., 2007). Login to comment

PMID: 16815813 [PubMed] Choudhuri S et al: "Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters."

No. Sentence Comment

573 Recently, Kondo et al. (2004) reported the effect of single nucleotide polymorphisms (SNPs) in ABCG2 gene on its localization, expression level, and transport activity of the BCRP protein. The cellular localization was identified using the wild-type and seven different SNP variants of BCRP protein (Val12Met, Gln141Lys, Ala149Pro, Arg163Lys, Gln166Glu, Pro269Ser, and Ser441Asn), following their expression in LLC-PK1 cells. Login to comment

PMID: 23379683 [PubMed] Lee Y et al: "Computational analysis and predictive modeling of polymorph descriptors."

No. Sentence Comment

126 It has distinctive features including racial differences; for instance, BCRP V12M, Q141K, P269S and Q126Stop were detected in Korean at frequencies of 23, 28, 0.2 and 1.9%, respectively [49]. Login to comment