ABCC6 explained

Multidrug resistance-associated protein 6 (MRP6) also known as ATP-binding cassette sub-family C member 6 (ABCC6) and multi-specific organic anion transporter E (MOAT-E) is a protein that in humans is encoded by the ABCC6 gene.[1] [2] [3] The protein encoded by the ABCC6 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters.

ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multidrug resistance.[4]

Pathology

Mutations in this protein cause pseudoxanthoma elasticum (PXE).[5] The most common mutations, R1141X and 23-29del, account for about 25% of the found mutations.[6] [7]

Premature atherosclerosis is also associated with mutations in the ABCC6 gene, even in those without PXE.[8]

Deficiency of Abcc6 in mouse models of ischemia leads to larger infarcts, which can be rescued by Abcc6 overexpression.[9]

Location

Abcc6 gene encodes an intracellular transporter associated with mitochondrial function, located in the mitochondrial-associated membrane (MAM), whereas its substrate can be located in either MAM, cytosol or ER.[10] Abcc6 is primarily expressed in liver and kidney,.[11] [12]

External links

Notes and References

  1. Kuss BJ, O'Neill GM, Eyre H, Doggett NA, Callen DF, Davey RA . ARA, a novel ABC transporter, is located at 16p13.1, is deleted in inv(16) leukemias, and is shown to be expressed in primitive hematopoietic precursors . Genomics . 51 . 3 . 455–8 . Oct 1998 . 9721217 . 10.1006/geno.1998.5349 .
  2. Meloni I, Rubegni P, De Aloe G, Bruttini M, Pianigiani E, Cusano R, Seri M, Mondillo S, Federico A, Bardelli AM, Andreassi L, Fimiani M, Renieri A . Pseudoxanthoma elasticum: Point mutations in the ABCC6 gene and a large deletion including also ABCC1 and MYH11 . Hum Mutat . 18 . 1 . 85 . Jul 2001 . 11439001 . 10.1002/humu.1157 . 23970082 . free .
  3. Web site: Entrez Gene: ABCC6 ATP-binding cassette, sub-family C (CFTR/MRP), member 6.
  4. O'Neill GM, Peters GB, Harvie RM, MacKenzie HB, Henness S, Davey RA . Amplification and expression of the ABC transporters ARA and MRP in a series of multidrug-resistant leukaemia cell sublines . Br. J. Cancer . 77 . 12 . 2076–80 . 1998 . 9649117 . 10.1038/bjc.1998.350. 2150375 .
  5. Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, Pasquali-Ronchetti I, Pope FM, Richards A, Terry S, Bercovitch L, de Paepe A, Boyd CD . Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum . Nat. Genet. . 25 . 2 . 223–7 . 2000 . 10835642 . 10.1038/76102 . 8883528 .
  6. Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD . A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum . Am. J. Hum. Genet. . 69 . 4 . 749–64 . 2001 . 11536079 . 10.1086/323704 . 1226061 .
  7. Pfendner EG, Vanakker O, Terry SF, Vourthis S, McAndrew PE, McClain MR, Fratta S, Marais AS, Hariri S, Coucke PJ, Ramsay M, Viljoen D, Terry PF, De Paepe A, Uitto J, Bercovitch LG . Mutation Detection in the ABCC6 Gene and Genotype-Phenotype Analysis in a Large International Case Series Affected by Pseudoxanthoma Elasticum . Journal of Medical Genetics. 44. 10. 621–8. 2007 . 17617515 . 2597973 . 10.1136/jmg.2007.051094 .
  8. Trip MD, Smulders YM, Wegman JJ, Hu X, Boer JM, ten Brink JB, Zwinderman AH, Kastelein JJ, Feskens EJ, Bergen AA . Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease . Circulation . 106 . 7 . 773–5 . 2002 . 12176944 . 10.1161/01.CIR.0000028420.27813.C0. free .
  9. Mungrue IN, Zhao P, Yao Y, Meng H, Rau C, Havel JV, Gorgels TG, Bergen AA, MacLellan WR, Drake TA, Boström KI, Lusis AJ . Abcc6 deficiency causes increased infarct size and apoptosis in a mouse cardiac ischemia-reperfusion model . Arterioscler Thromb Vasc Biol . 31 . 12 . 2806–12 . 2011 . 21979437 . 10.1161/ATVBAHA.111.237420 . 3227394.
  10. Martin LJ, Lau E, Singh H, Vergnes L, Tarling EJ, Mehrabian M, Mungrue I, Xiao S, Shih D, Castellani L, Ping P, Reue K, Stefani E, Drake TA, Bostrom K, Lusis AJ . ABCC6 localizes to the mitochondria-associated membrane . Circulation Research . 111 . 5 . 516–20 . 2012 . 22811557 . 10.1161/CIRCRESAHA.112.276667 . 3540978.
  11. Gorgels TG, Hu X, Scheffer GL, van der Wal AC, Toonstra J, de Jong PT, van Kuppevelt TH, Levelt CN, de Wolf A, Loves WJ, Scheper RJ, Peek R, Bergen AA . Disruption of Abcc6 in the mouse: novel insight in the pathogenesis of pseudoxanthoma elasticum . Human Molecular Genetics . 14 . 13 . 1763–73 . 2005 . 15888484 . 10.1093/hmg/ddi183. free .
  12. De Vilder EY, Hosen MJ, Vanakker OM . The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders. . BioMed Research International . 2015 . 648569 . 2015 . 26356190 . 10.1155/2015/648569 . 4555454. free .

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