SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis

The Journal of Biological Chemistry
Rebecca S GingerMartin R Green


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.


Dec 1, 1982·Journal of Cellular Physiology·J D LaskinI B Weinstein
Jun 1, 1993·The Journal of Investigative Dermatology·K IozumiB B Fuller
Aug 27, 1999·Biochemical and Biophysical Research Communications·K U Schallreuter, J M Wood
Apr 18, 2000·Human Molecular Genetics·R SudbrakA P Monaco
Dec 18, 2001·Journal of Photochemistry and Photobiology. B, Biology·K U Schallreuter, J M Wood
Jan 29, 2002·The Journal of Biological Chemistry·Ruth HalabanDaniel N Hebert
Jun 12, 2002·Molecular Biology of the Cell·Kun ChenSeth J Orlow
Feb 13, 2003·Human Genetics·Mark D ShriverRick A Kittles
Feb 26, 2003·Biochemistry·Tashi G KinjoPaul P M Schnetkamp
Apr 16, 2003·The Journal of Biological Chemistry·Kees VenemaJuan Pedro Donaire
Oct 14, 2003·PLoS Biology·Gregory S Barsh
Feb 13, 2004·Bioinformatics·Michele ClampGeoffrey J Barton
May 28, 2004·Molecular Biology and Evolution·Xinjiang Cai, Jonathan Lytton
Jul 22, 2004·Experimental Cell Research·Dustin R SmithBryan B Fuller
Dec 8, 2004·The Journal of Biological Chemistry·Kyeong-Jin KangPaul P M Schnetkamp
Mar 12, 2005·Pigment Cell Research·Andrea M Hall, Seth J Orlow
Oct 29, 2005·Nature·UNKNOWN International HapMap Consortium
Jan 20, 2006·Pigment Cell Research·Ning Wang, Daniel N Hebert
May 26, 2006·European Journal of Human Genetics : EJHG·Ian J Jackson
Jun 8, 2006·Molecular Biology and Evolution·Neskuts IzagirreSantos Alonso
Oct 7, 2006·Cell Calcium·Nick J Dolman, Alexei V Tepikin
Nov 4, 2006·Journal of Proteome Research·An ChiDonald F Hunt
Dec 22, 2006·Molecular Biology and Evolution·Heather L NortonMark D Shriver
Feb 17, 2007·The Journal of Biological Chemistry·Julio C ValenciaVincent J Hearing
Apr 21, 2007·Annals of the New York Academy of Sciences·L AnnunziatoG F Di Renzo
Jul 14, 2007·Current Opinion in Cell Biology·Graça RaposoDaniel F Cutler
Nov 14, 2007·American Journal of Human Genetics·Renee P StokowskiDavid R Cox
Aug 12, 2008·Channels·Haider F Altimimi, Paul P M Schnetkamp

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