ABCB5 p.Val115Glu
| Predicted by SNAP2: | A: N (93%), C: N (93%), D: N (57%), E: N (66%), F: N (93%), G: N (87%), H: N (82%), I: N (97%), K: N (66%), L: N (97%), M: N (87%), N: N (72%), P: N (61%), Q: N (78%), R: N (78%), S: N (87%), T: N (87%), W: N (66%), Y: N (93%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, W: N, Y: N, |
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[hide] Genetically determined ABCB5 functionality correla... Biochem Biophys Res Commun. 2013 Jul 5;436(3):536-42. doi: 10.1016/j.bbrc.2013.06.006. Epub 2013 Jun 12. Lin JY, Zhang M, Schatton T, Wilson BJ, Alloo A, Ma J, Qureshi AA, Frank NY, Han J, Frank MH
Genetically determined ABCB5 functionality correlates with pigmentation phenotype and melanoma risk.
Biochem Biophys Res Commun. 2013 Jul 5;436(3):536-42. doi: 10.1016/j.bbrc.2013.06.006. Epub 2013 Jun 12., [PMID:23770371]
Abstract [show]
ABCB5 is a multidrug resistance (MDR) member of the ATP-binding cassette (ABC) superfamily of active transporters and represents a marker for chemoresistant malignant melanoma-initiating cells. ABCB5 expression is closely linked to tumorigenicity and progression of diverse human malignancies, including melanoma, and is functionally required for tumor growth. Here, we genotyped 585 melanoma cases and 605 age-matched controls for 44 ABCB5 tagging single nucleotide polymorphisms (SNPs) to span a region covering 108.2kb of the gene on the 7p21.1 locus. We identified three SNPs that were associated with decreased melanoma risk in additive models: rs10231520 (OR: 0.83, 95% CI: 0.70-0.98), rs17817117 (OR: 0.82, 95% CI: 0.68-0.98), and rs2301641 (OR: 0.83, 95% CI: 0.69-0.98). Additionally, the rs2301641 SNP was associated with non-red compared to red hair color (OR: 0.38, 95% CI: 0.14-1.03) in controls. Twelve human melanoma cell lines were genotyped for the rs2301641 SNP, which encodes a non-synonymous ABCB5 amino acid change (K115E). Functional studies revealed that the E form associated with lower melanoma risk correlated significantly with decreased ABCB5 transport capacity (P<0.01) and increased melanin production (P<0.05). Our results identify novel associations of the ABCB5 K115E polymorphism with human pigmentation phenotype and melanoma risk and point to potential functional roles of ABCB5 in melanomagenesis. Moreover, they provide a first example that functional variation in a prospective cancer stem cell marker can be associated with disease risk for the corresponding malignancy.
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No. Sentence Comment
5 Twelve human melanoma cell lines were genotyped for the rs2301641 SNP, which encodes a non-synonymous ABCB5 amino acid change (K115E).
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ABCB5 p.Val115Glu 23770371:5:127
status: NEW7 Our results identify novel associations of the ABCB5 K115E polymorphism with human pigmentation phenotype and melanoma risk and point to potential functional roles of ABCB5 in melanomagenesis.
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ABCB5 p.Val115Glu 23770371:7:53
status: NEW30 Among single nucleotide polymorphisms (SNPs) of the ABCB5 gene, several, including the rs2301641 SNP, which encodes a non-synonymous ABCB5 amino acid change (K115E), have been predicted to be relevant to ABCB5 function based on bioinformatic analyses [17].
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ABCB5 p.Val115Glu 23770371:30:158
status: NEW34 We confirmed the direct association of one of these SNPs, rs2301641 (K115E), with ABCB5 function and, furthermore, uncovered a novel association of ABCB5 with pigmentation.
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ABCB5 p.Val115Glu 23770371:34:69
status: NEW112 3.5. Association between rs2301641 genotype and ABCB5-mediated Rh-123 efflux capacity The SNP rs2301641 encodes a non-synonymous ABCB5 amino acid change (K115E).
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ABCB5 p.Val115Glu 23770371:112:154
status: NEW126 Importantly, evaluation of relative Rh-123 efflux capacities in melanoma cell lines genotyped for the rs2301641 ABCB5 SNP (K115E) revealed that the SNP allele G (Glu [E]) was associated with markedly lower, 89%-reduced Rh-123 efflux capacity compared to the SNP allele A (Lys [K]) (P < 0.01, Fig. 3A).
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ABCB5 p.Val115Glu 23770371:126:123
status: NEW128 3.6. Association between rs2301641 genotype and pigmentation Given the additional association of the rs2301641 ABCB5 SNP with non-red compared to red hair color (OR: 0.38, 95% CI: 0.141.03) in control subjects, we measured melanin concentration, a measure of pigmentation, in eleven human melanoma cell lines genotyped for this SNP (K115E).
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ABCB5 p.Val115Glu 23770371:128:333
status: NEW134 (A) Relative Rh-123 efflux capacities in melanoma cell lines genotyped for the rs2301641 ABCB5 SNP (K115E) (means &#b1; SE; // P < 0.01).
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ABCB5 p.Val115Glu 23770371:134:100
status: NEW135 (B) Relative pigmentation in melanoma cell lines genotyped for the rs2301641 ABCB5 SNP (K115E) (means &#b1; SE; / P < 0.05).
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ABCB5 p.Val115Glu 23770371:135:88
status: NEWX
ABCB5 p.Val115Glu 23770371:135:100
status: NEW137 Discussion In this study, we have identified three SNPs of the ABCB5 gene associated with melanoma risk, and shown for one SNP (rs2301641), which encodes a non-synonymous ABCB5 amino acid change (K115E), that the variant genotype that confers decreased melanoma risk is associated with lower ABCB5 protein function.
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ABCB5 p.Val115Glu 23770371:137:196
status: NEW141 Bioinformatic in silico analyses of ABCB5 gene polymorphisms had previously predicted the K115E amino acid substitution encoded by the rs2301641 SNP, which changes a positively charged amino acid to a negatively charged one and localizes to an extracellular loop of the ABCB5 protein [4], to be potentially deleterious to ABCB5 molecular function [17], a notion now for the first time experimentally supported by our study.
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ABCB5 p.Val115Glu 23770371:141:90
status: NEW136 (B) Relative pigmentation in melanoma cell lines genotyped for the rs2301641 ABCB5 SNP (K115E) (means &#b1; SE; / P < 0.05).
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ABCB5 p.Val115Glu 23770371:136:88
status: NEW138 Discussion In this study, we have identified three SNPs of the ABCB5 gene associated with melanoma risk, and shown for one SNP (rs2301641), which encodes a non-synonymous ABCB5 amino acid change (K115E), that the variant genotype that confers decreased melanoma risk is associated with lower ABCB5 protein function.
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ABCB5 p.Val115Glu 23770371:138:196
status: NEW142 Bioinformatic in silico analyses of ABCB5 gene polymorphisms had previously predicted the K115E amino acid substitution encoded by the rs2301641 SNP, which changes a positively charged amino acid to a negatively charged one and localizes to an extracellular loop of the ABCB5 protein [4], to be potentially deleterious to ABCB5 molecular function [17], a notion now for the first time experimentally supported by our study.
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ABCB5 p.Val115Glu 23770371:142:90
status: NEW