ABCC4 p.Gly538Ala
| Predicted by SNAP2: | A: D (80%), C: D (80%), D: D (91%), E: D (95%), F: D (91%), H: D (91%), I: D (91%), K: D (95%), L: D (91%), M: D (91%), N: D (85%), P: D (91%), Q: D (91%), R: D (95%), S: D (75%), T: D (91%), V: D (91%), W: D (95%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Signatures of recent positive selection at the ATP... Hum Mol Genet. 2007 Jun 1;16(11):1367-80. Epub 2007 Apr 5. Wang Z, Wang J, Tantoso E, Wang B, Tai AY, Ooi LL, Chong SS, Lee CG
Signatures of recent positive selection at the ATP-binding cassette drug transporter superfamily gene loci.
Hum Mol Genet. 2007 Jun 1;16(11):1367-80. Epub 2007 Apr 5., [PMID:17412754]
Abstract [show]
Members of the ATP-binding cassette (ABC) superfamily of transporters have been implicated as major players in drug response. Single nucleotide polymorphisms (SNPs) in the ABC transporter genes may account for variation in drug response between individuals. Given the abundance of SNPs within the human genome, identification of functionally important SNPs is difficult. Here, we utilized signatures of recent positive selection (RPS) to identify SNPs in ABC genes that have potential functional significance by using the long-range-haplotype test to search for signatures of RPS at 18 ABC genes involved in drug transport. From the genotype data of these 18 ABC genes in four populations extracted from the HapMap database, at least one SNP in each of these genes displayed genomic signatures of RPS in at least one population. However, only 13 SNPs in 10 ABC genes from three populations retained statistical significance after Type I error reduction. The functional significance of six of these RPS SNPs, including those that failed multiple testing correction (MTC), has been reported previously. We experimentally confirmed a functional effect for two SNPs, including one that failed to show evidence of RPS after MTC. These observations suggest that Type I error reduction may inadvertently increase Type II error. Although the remaining positively selected SNPs have yet to be functionally validated, our study illustrates the feasibility of using this strategy to identify SNPs within 'adaptive' genes that may confer functional effect, prior to testing their roles in individual/population drug response variation or in complex disease susceptibility.
Comments [show]
None has been submitted yet.
No. Sentence Comment
203 Recently, the ABCC11 SNP e5/G538A was found to be a determinant of earwax type, with the G- and A-alleles corresponding to wet and dry earwax types (64).
X
ABCC4 p.Gly538Ala 17412754:203:28
status: NEW208 All other HapMap genotyped ABCC11SNPs are monomorphic in the Asian populations (Supplementary Material, Table S2), thus preventing the LRH test from being performed on SNP e5/G538A.
X
ABCC4 p.Gly538Ala 17412754:208:175
status: NEW223 The only sole HapMap genotyped, high frequency SNP that did not show evidence of RPS in this study is the ABCC11 SNP e5/G538A.
X
ABCC4 p.Gly538Ala 17412754:223:120
status: NEW202 Recently, the ABCC11 SNP e5/G538A was found to be a determinant of earwax type, with the Gand A-alleles corresponding to wet and dry earwax types (64).
X
ABCC4 p.Gly538Ala 17412754:202:28
status: NEW207 All other HapMap genotyped ABCC11SNPs are monomorphic in the Asian populations (Supplementary Material, Table S2), thus preventing the LRH test from being performed on SNP e5/G538A.
X
ABCC4 p.Gly538Ala 17412754:207:175
status: NEW222 The only sole HapMap genotyped, high frequency SNP that did not show evidence of RPS in this study is the ABCC11 SNP e5/G538A.
X
ABCC4 p.Gly538Ala 17412754:222:120
status: NEW[hide] Redox regulation of multidrug resistance in cancer... Antioxid Redox Signal. 2009 Jan;11(1):99-133. Kuo MT
Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities.
Antioxid Redox Signal. 2009 Jan;11(1):99-133., [PMID:18699730]
Abstract [show]
The development of multidrug resistance to cancer chemotherapy is a major obstacle to the effective treatment of human malignancies. It has been established that membrane proteins, notably multidrug resistance (MDR), multidrug resistance protein (MRP), and breast cancer resistance protein (BCRP) of the ATP binding cassette (ABC) transporter family encoding efflux pumps, play important roles in the development of multidrug resistance. Overexpression of these transporters has been observed frequently in many types of human malignancies and correlated with poor responses to chemotherapeutic agents. Evidence has accumulated showing that redox signals are activated in response to drug treatments that affect the expression and activity of these transporters by multiple mechanisms, including (a) conformational changes in the transporters, (b) regulation of the biosynthesis cofactors required for the transporter's function, (c) regulation of the expression of transporters at transcriptional, posttranscriptional, and epigenetic levels, and (d) amplification of the copy number of genes encoding these transporters. This review describes various specific factors and their relevant signaling pathways that are involved in the regulation. Finally, the roles of redox signaling in the maintenance and evolution of cancer stem cells and their implications in the development of intrinsic and acquired multidrug resistance in cancer chemotherapy are discussed.
Comments [show]
None has been submitted yet.
No. Sentence Comment
117 Interestingly, a single-nucleotide polymorphism in MRP8 (G538A) is associated with the dry-earwax phenotype in humans, and GA and GG, with the wet type (286) and colostrum and cerumen section (177).
X
ABCC4 p.Gly538Ala 18699730:117:57
status: NEW