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.[5][6][7] The protein encoded by the ABCC6 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters.[5]
Quick Facts Identifiers, Aliases ...
ABCC6 |
---|
|
Identifiers |
---|
Aliases | ABCC6, ABC34, ARA, EST349056, GACI2, MLP1, MOAT-E, MOATE, MRP6, PXE, PXE1, URG7, ATP binding cassette subfamily C member 6 |
---|
External IDs | OMIM: 603234; MGI: 1351634; HomoloGene: 55559; GeneCards: ABCC6; OMA:ABCC6 - orthologs |
---|
|
|
|
|
|
Wikidata |
|
Close
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.[8]
Mutations in this protein cause pseudoxanthoma elasticum (PXE).[9] The most common mutations, R1141X and 23-29del, account for about 25% of the found mutations.[10][11]
Premature atherosclerosis is also associated with mutations in the ABCC6 gene, even in those without PXE.[12]
Deficiency of Abcc6 in mouse models of ischemia leads to larger infarcts, which can be rescued by Abcc6 overexpression.[13]
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.[14]
Abcc6 is primarily expressed in liver and kidney,.[15][16]
Kuss BJ, O'Neill GM, Eyre H, Doggett NA, Callen DF, Davey RA (Oct 1998). "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. doi:10.1006/geno.1998.5349. PMID 9721217.
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 (Jul 2001). "Pseudoxanthoma elasticum: Point mutations in the ABCC6 gene and a large deletion including also ABCC1 and MYH11". Hum Mutat. 18 (1): 85. doi:10.1002/humu.1157. PMID 11439001. S2CID 23970082.
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 (2000). "Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum". Nat. Genet. 25 (2): 223–7. doi:10.1038/76102. PMID 10835642. S2CID 8883528.
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 (2001). "A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum". Am. J. Hum. Genet. 69 (4): 749–64. doi:10.1086/323704. PMC 1226061. PMID 11536079.
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 (2007). "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. doi:10.1136/jmg.2007.051094. PMC 2597973. PMID 17617515.
Mungrue IN, Zhao P, Yao Y, Meng H, Rau C, Havel JV, Gorgels TG, Bergen AA, MacLellan WR, Drake TA, Boström KI, Lusis AJ (2011). "Abcc6 deficiency causes increased infarct size and apoptosis in a mouse cardiac ischemia-reperfusion model". Arterioscler Thromb Vasc Biol. 31 (12): 2806–12. doi:10.1161/ATVBAHA.111.237420. PMC 3227394. PMID 21979437.
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 (2012). "ABCC6 localizes to the mitochondria-associated membrane". Circulation Research. 111 (5): 516–20. doi:10.1161/CIRCRESAHA.112.276667. PMC 3540978. PMID 22811557.
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 (2005). "Disruption of Abcc6 in the mouse: novel insight in the pathogenesis of pseudoxanthoma elasticum". Human Molecular Genetics. 14 (13): 1763–73. doi:10.1093/hmg/ddi183. PMID 15888484.