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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2008-2-25
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pubmed:abstractText |
A non-synonymous single nucleotide polymorphism in the human SLC24A5 gene is associated with natural human skin color variation. Multiple sequence alignments predict that this gene encodes a member of the potassium-dependent sodium-calcium exchanger family denoted NCKX5. In cultured human epidermal melanocytes we show using affinity-purified antisera that native human NCKX5 runs as a triplet of approximately 43 kDa on SDS-PAGE and is partially localized to the trans-Golgi network. Removal of the NCKX5 protein through small interfering RNA-mediated knockdown disrupts melanogenesis in human and murine melanocytes, causing a significant reduction in melanin pigment production. Using a heterologous expression system, we confirm for the first time that NCKX5 possesses the predicted exchanger activity. Site-directed mutagenesis of NCKX5 and NCKX2 in this system reveals that the non-synonymous single nucleotide polymorphism in SLC24A5 alters a residue that is important for NCKX5 and NCKX2 activity. We suggest that NCKX5 directly regulates human epidermal melanogenesis and natural skin color through its intracellular potassium-dependent exchanger activity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:AskewSarah ESE,
pubmed-author:DaddTonyT,
pubmed-author:FerdinandoDudleyD,
pubmed-author:GingerRebecca SRS,
pubmed-author:GreenMartin RMR,
pubmed-author:KaziShubanaS,
pubmed-author:OgborneRichard MRM,
pubmed-author:SchnetkampPaul P MPP,
pubmed-author:SmithAdrian MAM,
pubmed-author:SzerencseiRobert TRT,
pubmed-author:WilsonStephenS,
pubmed-author:WinkfeinRobert JRJ
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pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5486-95
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pubmed:dateRevised |
2008-10-20
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pubmed:meshHeading |
pubmed-meshheading:18166528-Animals,
pubmed-meshheading:18166528-Antiporters,
pubmed-meshheading:18166528-Calcium,
pubmed-meshheading:18166528-Cell Line, Tumor,
pubmed-meshheading:18166528-Golgi Apparatus,
pubmed-meshheading:18166528-Humans,
pubmed-meshheading:18166528-Ion Transport,
pubmed-meshheading:18166528-Male,
pubmed-meshheading:18166528-Melanins,
pubmed-meshheading:18166528-Melanocytes,
pubmed-meshheading:18166528-Mice,
pubmed-meshheading:18166528-Pigmentation,
pubmed-meshheading:18166528-Polymorphism, Single Nucleotide,
pubmed-meshheading:18166528-Potassium,
pubmed-meshheading:18166528-Sodium,
pubmed-meshheading:18166528-Sodium-Calcium Exchanger
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pubmed:year |
2008
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pubmed:articleTitle |
SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis.
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pubmed:affiliation |
Unilever Corporate Research, Colworth Science Park, Sharnbrook, Bedfordshire, MK44 1LQ, England, United Kingdom. rebecca.ginger@unilever.com
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pubmed:publicationType |
Journal Article
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