ABCC6

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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
Gene location (Human)
Chromosome 16 (human)
Chr. Chromosome 16 (human)[1]
Chromosome 16 (human)
Genomic location for ABCC6
Genomic location for ABCC6
Band 16p13.11 Start 16,148,928 bp[1]
End 16,223,522 bp[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001079528
NM_001171
NM_001351800

NM_018795

RefSeq (protein)

NP_001072996
NP_001162
NP_001338729

NP_061265

Location (UCSC) Chr 16: 16.15 – 16.22 Mb Chr 16: 45.97 – 46.03 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

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]

Pathology[edit]

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]

Location[edit]

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]

Signaling pathways[edit]

It has been observed less Smad1/5/8 activation in the presence of Abcc6 than in mice lacking that gene in liver, kidney, heart, muscle, aorta and lungs.[17] ALK1, ALK2 and ALK3 expression are higher in kidneys, but lower in liver, with functional Abcc6 and its presence causes higher expression of BMP2 in kidney and a decrease in its expression in liver.[17] In the presence of Abcc6, BMP-4, BMP-6 and BMP-7 expression is increased in kidney and decreased in liver.[17] Abcc6 deficient mice show higher BMP activation in the heart.[13]

References[edit]

  1. ^ a b c ENSG00000091262 GRCh38: Ensembl release 89: ENSG00000275331, ENSG00000091262 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030834 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b 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. 
  6. ^ 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. 
  7. ^ "Entrez Gene: ABCC6 ATP-binding cassette, sub-family C (CFTR/MRP), member 6". 
  8. ^ O'Neill GM, Peters GB, Harvie RM, MacKenzie HB, Henness S, Davey RA (1998). "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. doi:10.1038/bjc.1998.350. PMC 2150375Freely accessible. PMID 9649117. 
  9. ^ 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. 
  10. ^ 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 1226061Freely accessible. PMID 11536079. 
  11. ^ 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 2597973Freely accessible. PMID 17617515. 
  12. ^ Trip MD, Smulders YM, Wegman JJ, Hu X, Boer JM, ten Brink JB, Zwinderman AH, Kastelein JJ, Feskens EJ, Bergen AA (2002). "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. doi:10.1161/01.CIR.0000028420.27813.C0. PMID 12176944. 
  13. ^ a b 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 3227394Freely accessible. PMID 21979437. 
  14. ^ 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 3540978Freely accessible. PMID 22811557. 
  15. ^ 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. 
  16. ^ De Vilder EY, Hosen MJ, Vanakker OM (2015). "The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders". Biomed Research International. 2015: 648569. doi:10.1155/2015/648569. PMC 4555454Freely accessible. PMID 26356190. 
  17. ^ a b c Blázquez-Medela AM, Guihard PJ, Yao J, Jumabay M, Lusis AJ, Boström KI, Yao Y (2015). "ABCC6 deficiency is associated with activation of BMP signaling in liver and kidney". FEBS Open Bio. 5: 257–63. doi:10.1016/j.fob.2015.03.009. PMC 4398664Freely accessible. PMID 25893161. 

External links[edit]