ABCB1 p.Pro996Gln
| Predicted by SNAP2: | A: D (75%), C: D (80%), D: D (91%), E: D (85%), F: D (85%), G: D (80%), H: D (85%), I: D (85%), K: D (85%), L: D (85%), M: D (80%), N: D (80%), Q: D (85%), R: D (85%), S: D (75%), T: D (75%), V: D (80%), W: D (85%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Molecular evolutionary analysis of ABCB5: the ance... PLoS One. 2011 Jan 27;6(1):e16318. Moitra K, Scally M, McGee K, Lancaster G, Gold B, Dean M
Molecular evolutionary analysis of ABCB5: the ancestral gene is a full transporter with potentially deleterious single nucleotide polymorphisms.
PLoS One. 2011 Jan 27;6(1):e16318., [PMID:21298007]
Abstract [show]
BACKGROUND: ABCB5 is a member of the ABC protein superfamily, which includes the transporters ABCB1, ABCC1 and ABCG2 responsible for causing drug resistance in cancer patients and also several other transporters that have been linked to human disease. The ABCB5 full transporter (ABCB5.ts) is expressed in human testis and its functional significance is presently unknown. Another variant of this transporter, ABCB5 beta possess a "half-transporter-like" structure and is expressed in melanoma stem cells, normal melanocytes, and other types of pigment cells. ABCB5 beta has important clinical implications, as it may be involved with multidrug resistance in melanoma stem cells, allowing these stem cells to survive chemotherapeutic regimes. METHODOLOGY/PRINCIPAL FINDINGS: We constructed and examined in detail topological structures of the human ABCB5 protein and determined in-silico the cSNPs (coding single nucleotide polymorphisms) that may affect its function. Evolutionary analysis of ABCB5 indicated that ABCB5, ABCB1, ABCB4, and ABCB11 share a common ancestor, which began duplicating early in the evolutionary history of chordates. This suggests that ABCB5 has evolved as a full transporter throughout its evolutionary history. CONCLUSIONS/SIGNIFICANCE: From our in-silco analysis of cSNPs we found that a large number of non-synonymous cSNPs map to important functional regions of the protein suggesting that these SNPs if present in human populations may play a role in diseases associated with ABCB5. From phylogenetic analyses, we have shown that ABCB5 evolved as a full transporter throughout its evolutionary history with an absence of any major shifts in selection between the various lineages suggesting that the function of ABCB5 has been maintained during mammalian evolution. This finding would suggest that ABCB5 beta may have evolved to play a specific role in human pigment cells and/or melanoma cells where it is predominantly expressed.
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No. Sentence Comment
130 With the aid of SIFT analysis we found that a number of the substitutions were not tolerated including: F155V, R260K, Q262K, I369V, D370G, G810V, P996Q, C1054W, K1056E, E1124K and D1187G.
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ABCB1 p.Pro996Gln 21298007:130:146
status: NEW204 In silico prediction of functional significance of ABCB.ts non-synonymous cSNPs calculated using Panther. Substitution subPSEC score P66L 25.10163 T131I 23.1368 F155V 27.05629 R260K 22.69866 Q262K 23.89135 I369V 23.98202 D370G 24.70914 M446T 23.64169 K560E 26.12726 K669R 23.1384 G810V 24.6663 A857T 22.52579 Q905H 24.03142 A915T 23.86813 E970K 22.81761 P996Q 4.62436 C1054W 28.89455 I1093T 24.64248 E1124K 23.58989 D1187G 26.60494 doi:10.1371/journal.pone.0016318.t004 Table 3.
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ABCB1 p.Pro996Gln 21298007:204:354
status: NEW