Cloning, Sequence and Functional Analysis of Goat ATP-binding Cassette Transporter G2 (ABCG2)

Wu, Hui; Luo, Jun; Wu, Ning; Matand, Kanyand; Zhang, Li Juan; Han, Xue; Yang, Bao Jin

doi:10.1007/s12033-007-9024-5

Cited by 18 publications

(13 citation statements)

References 31 publications

(38 reference statements)

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“…Motif Scan was also used to detect functional domains. Several phosphorylation sites and glycosylation sites were present, which may be important for targeting of the protein to the membrane [19]. In the full transporter, 14 N-glycosylation sites were found, out of which 2 sites (aa 85–88, 91–94) may be important for targeting of the transporter to the membrane (fig.…”

Section: Resultsmentioning

confidence: 99%

“…Two or more alpha-helices wound around each other in a symmetrical manner make up the basic “coiled–coil” structure [22]. Coiled-coils have been predicted to exist at the N-terminus of the goat half-transporter ABCG2 and the investigators have discussed the possibility that these domains may be involved in oligomerization functions [23]. A unique feature of the ABCB5 beta form is that it has 2 NBDs (first NBD lacking the Walker A) rather than the conventional 1 NBD, which is usually present in half-transporters.…”

Section: Resultsmentioning

confidence: 99%

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Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms

et al. 2011

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BackgroundABCB5 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 posses 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 FindingsWe 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/SignificanceFrom 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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms

et al. 2011

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“…Despite being a highly conserved transporter (Wu et al 2008), there is an increasing number of studies that describe differences in function and specificity of ABCG2 in different species (Schnepf & Zolk 2013;Wassermann, Halwachs, Baumann, et al 2013). In vitro cell models have been generated for the identification of ABCG2 substrates using transcellular transport mediated by the caprine and bovine ABCG2 and its Y581S variant Wassermann, Halwachs, Baumann, et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Novelin vitrosystems for prediction of veterinary drug residues in ovine milk and dairy products

González-Lobato

Real

Herrero

et al. 2014

Food Additives & Contaminants: Part A

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A new in vitro tool was developed for the identification of veterinary substrates of the main drug transporter in the mammary gland. These drugs have a much higher chance of being concentrated into ovine milk and thus should be detectable in dairy products. Complementarily, a cell model for the identification of compounds that can inhibit the secretion of drugs into ovine milk, and thus reduce milk residues, was also generated. The ATP-binding cassette transporter G2 (ABCG2) is responsible for the concentration of its substrates into milk. The need to predict potential drug residues in ruminant milk has prompted the development of in vitro cell models over-expressing ABCG2 for these species to detect veterinary drugs that interact with this transporter. Using these models, several substrates for bovine and caprine ABCG2 have been found, and differences in activity between species have been reported. However, despite being of great toxicological relevance, no suitable in vitro model to predict substrates of ovine ABCG2 was available. New MDCKII and MEF3.8 cell models over-expressing ovine ABCG2 were generated for the identification of substrates and inhibitors of ovine ABCG2. Five widely used veterinary antibiotics (marbofloxacin, orbifloxacin, sarafloxacin, danofloxacin and difloxacin) were discovered as new substrates of ovine ABCG2. These results were confirmed for the bovine transporter and its Y581S variant using previously generated cell models. In addition, the avermectin doramectin was described as a new inhibitor of ruminant ABCG2. This new rapid assay to identify veterinary drugs that can be concentrated into ovine milk will potentially improve detection and monitoring of veterinary drug residues in ovine milk and dairy products.

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“…ABCG2 is expressed several tissue including mammary gland and it is reported that the level of expression is elevated in lactation period in some monogastrics, goats and dairy cows [9][10][11] . Due to its function and near chromosomal location to an important QTL region effects on milk production traits in cattle [12,13] , researches have been focused on associations between mutations occur in the ABCG2 gene and milk production traits.…”

Section: Makale Kodu (Article Code): Kvfd-2014-8898mentioning

confidence: 99%

Investigation of Polymorphisms on ABCG2, AA-NAT and FABP3 Genes in the Kıvırcık Sheep Reared in Three Different Provinces of Turkey

Öner¹,

Orman²,

Üstüner³

et al. 2014

Kafkas Univ Vet Fak Derg

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SummaryIn this study mutations located in intron 5 of ABCG2, exon 3 of AA-NAT and exon 2 of FAB3 genes were investigated by PCR based methods in the Kıvırcık sheep sampled from Bursa, Manisa, and İstanbul provinces of Turkey. All loci investigated were found as polymorphic. While in the ABCG2 and FABP3 loci two alleles and three genotypes were found, in the AA-NAT locus two alleles and two genotypes were detected. In ABCG2 locus allele "-", in AA-NAT allele A, in FABP3 locus allele G were observed as predominant. The frequency values of the predominat alleles at ABCG2, AA-NAT and FABP3 loci were found 0.60, 0.87 and 0.58, respectively. While the whole population investigated exhibits deviation from the Hardy-Weinberg equilibrium for ABCG2 and FABP3 loci, was found at Hardy-Weinberg equilibrium for AA-NAT locus. Keywords: ABCG2, AA-NAT, FABP3, Polymorphism, SheepTürkiye'nin Üç Faklı İlinde Yetiştirilen Kıvırcık Koyunlarda ABCG2, AA-NAT ve FABP3 Genlerindeki Polimorfizmlerin İncelenmesi ÖzetBu çalışmada Türkiye'nin Bursa, Manisa ve İstanbul illerinden örneklenen Kıvırcık koyunlarında ABCG2 geninin 5.intron, AA-NAT geninin 3. ekzonunda ve FABP3 geninin 2. ekzonunda bulunan mutasyonlar PCR tabanlı yöntemlerle incelenmiştir. İncelenen tüm lokuslar polimorfik bulunmuştur. ABCG2 ve FABP3 lokuslarında iki allel ve üç genotip belirlenirken, AA-NAT lokusunda iki allel ve iki genotip belirlenmiştir. ABCG2 lokusunda "-" alleli, AA-NAT lokusunda A alleli ve FABP3 lokusunda G allellinin predominant olduğu gözlenmiştir. ABCG2, AA-NAT ve FABP3 lokuslarındaki predominant allelerin frekans değerleri sırasıyla 0.60, 0.87 ve 0.58 olarak bulunmuştur. İncelenen populayonun tamamı ABCG2 ve FABP3 lokusları bakımından Hardy-Weinberg dengesinden sapma gösterirken AA-NAT lokusu bakımından dengede bulunmuştur.

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Cloning, Sequence and Functional Analysis of Goat ATP-binding Cassette Transporter G2 (ABCG2)

Cited by 18 publications

References 31 publications

Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms

Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms

Novelin vitrosystems for prediction of veterinary drug residues in ovine milk and dairy products

Investigation of Polymorphisms on ABCG2, AA-NAT and FABP3 Genes in the Kıvırcık Sheep Reared in Three Different Provinces of Turkey

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