Multidrug resistance-associated protein 6

Details

Name
Multidrug resistance-associated protein 6
Synonyms
  • Anthracycline resistance-associated protein
  • ARA
  • ATP-binding cassette sub-family C member 6
  • MOAT-E
  • MRP6
  • Multi-specific organic anion transporter E
Gene Name
ABCC6
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037249|Multidrug resistance-associated protein 6
MAAPAEPCAGQGVWNQTEPEPAATSLLSLCFLRTAGVWVPPMYLWVLGPIYLLFIHHHGR
GYLRMSPLFKAKMVLGFALIVLCTSSVAVALWKIQQGTPEAPEFLIHPTVWLTTMSFAVF
LIHTERKKGVQSSGVLFGYWLLCFVLPATNAAQQASGAGFQSDPVRHLSTYLCLSLVVAQ
FVLSCLADQPPFFPEDPQQSNPCPETGAAFPSKATFWWVSGLVWRGYRRPLRPKDLWSLG
RENSSEELVSRLEKEWMRNRSAARRHNKAIAFKRKGGSGMKAPETEPFLRQEGSQWRPLL
KAIWQVFHSTFLLGTLSLIISDVFRFTVPKLLSLFLEFIGDPKPPAWKGYLLAVLMFLSA
CLQTLFEQQNMYRLKVLQMRLRSAITGLVYRKVLALSSGSRKASAVGDVVNLVSVDVQRL
TESVLYLNGLWLPLVWIVVCFVYLWQLLGPSALTAIAVFLSLLPLNFFISKKRNHHQEEQ
MRQKDSRARLTSSILRNSKTIKFHGWEGAFLDRVLGIRGQELGALRTSGLLFSVSLVSFQ
VSTFLVALVVFAVHTLVAENAMNAEKAFVTLTVLNILNKAQAFLPFSIHSLVQARVSFDR
LVTFLCLEEVDPGVVDSSSSGSAAGKDCITIHSATFAWSQESPPCLHRINLTVPQGCLLA
VVGPVGAGKSSLLSALLGELSKVEGFVSIEGAVAYVPQEAWVQNTSVVENVCFGQELDPP
WLERVLEACALQPDVDSFPEGIHTSIGEQGMNLSGGQKQRLSLARAVYRKAAVYLLDDPL
AALDAHVGQHVFNQVIGPGGLLQGTTRILVTHALHILPQADWIIVLANGAIAEMGSYQEL
LQRKGALMCLLDQARQPGDRGEGETEPGTSTKDPRGTSAGRRPELRRERSIKSVPEKDRT
TSEAQTEVPLDDPDRAGWPAGKDSIQYGRVKATVHLAYLRAVGTPLCLYALFLFLCQQVA
SFCRGYWLSLWADDPAVGGQQTQAALRGGIFGLLGCLQAIGLFASMAAVLLGGARASRLL
FQRLLWDVVRSPISFFERTPIGHLLNRFSKETDTVDVDIPDKLRSLLMYAFGLLEVSLVV
AVATPLATVAILPLFLLYAGFQSLYVVSSCQLRRLESASYSSVCSHMAETFQGSTVVRAF
RTQAPFVAQNNARVDESQRISFPRLVADRWLAANVELLGNGLVFAAATCAVLSKAHLSAG
LVGFSVSAALQVTQTLQWVVRNWTDLENSIVSVERMQDYAWTPKEAPWRLPTCAAQPPWP
QGGQIEFRDFGLRYRPELPLAVQGVSFKIHAGEKVGIVGRTGAGKSSLASGLLRLQEAAE
GGIWIDGVPIAHVGLHTLRSRISIIPQDPILFPGSLRMNLDLLQEHSDEAIWAALETVQL
KALVASLPGQLQYKCADRGEDLSVGQKQLLCLARALLRKTQILILDEATAAVDPGTELQM
QAMLGSWFAQCTVLLIAHRLRSVMDCARVLVMDKGQVAESGSPAQLLAQKGLFYRLAQES
GLV
Number of residues
1503
Molecular Weight
164904.81
Theoretical pI
8.55
GO Classification
Functions
ATP binding / ATPase activity, coupled to transmembrane movement of substances / transporter activity
Processes
response to drug / transmembrane transport / transport / visual perception
Components
apical plasma membrane / basolateral plasma membrane / endoplasmic reticulum membrane / integral component of membrane / lateral plasma membrane / nucleus / plasma membrane
General Function
Transporter activity
Specific Function
Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS).Isoform 2: Inhibits TNF-alpha-mediated apoptosis through blocking one or more caspases.
Pfam Domain Function
Transmembrane Regions
32-52 73-93 99-119 132-149 168-188 303-323 350-370 427-447 451-471 534-554 576-596 940-960 998-1018 1062-1082 1084-1104 1176-1196 1199-1219
Cellular Location
Basolateral cell membrane
Gene sequence
>lcl|BSEQ0019453|Multidrug resistance-associated protein 6 (ABCC6)
ATGGCCGCGCCTGCTGAGCCCTGCGCGGGGCAGGGGGTCTGGAACCAGACAGAGCCTGAA
CCTGCCGCCACCAGCCTGCTGAGCCTGTGCTTCCTGAGAACAGCAGGGGTCTGGGTACCC
CCCATGTACCTCTGGGTCCTTGGTCCCATCTACCTCCTCTTCATCCACCACCATGGCCGG
GGCTACCTCCGGATGTCCCCACTCTTCAAAGCCAAGATGGTAGCTGCCATCCCTGGGAGC
CTGGAACCAGGCAATGTTCGGGGGAGGCAGGGGACAGGCTGGAACCTGGTGAAGTCTTAA
Chromosome Location
16
Locus
16p13.1
External Identifiers
ResourceLink
UniProtKB IDO95255
UniProtKB Entry NameMRP6_HUMAN
GenBank Protein ID3928849
GenBank Gene IDAF076622
HGNC IDHGNC:57
General References
  1. Belinsky MG, Kruh GD: MOAT-E (ARA) is a full-length MRP/cMOAT subfamily transporter expressed in kidney and liver. Br J Cancer. 1999 Jul;80(9):1342-9. [Article]
  2. Kool M, van der Linden M, de Haas M, Baas F, Borst P: Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. Cancer Res. 1999 Jan 1;59(1):175-82. [Article]
  3. Lian Z, Liu J, Pan J, Satiroglu Tufan NL, Zhu M, Arbuthnot P, Kew M, Clayton MM, Feitelson MA: A cellular gene up-regulated by hepatitis B virus-encoded X antigen promotes hepatocellular growth and survival. Hepatology. 2001 Jul;34(1):146-57. [Article]
  4. Armentano MF, Ostuni A, Infantino V, Iacobazzi V, Castiglione Morelli MA, Bisaccia F: Identification of a New Splice Variant of the Human ABCC6 Transporter. Biochem Res Int. 2008;2008:912478. doi: 10.1155/2008/912478. Epub 2008 Oct 16. [Article]
  5. Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295-308. [Article]
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  8. Ilias A, Urban Z, Seidl TL, Le Saux O, Sinko E, Boyd CD, Sarkadi B, Varadi A: Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem. 2002 May 10;277(19):16860-7. Epub 2002 Mar 5. [Article]
  9. Uitto J, Pulkkinen L, Ringpfeil F: Molecular genetics of pseudoxanthoma elasticum: a metabolic disorder at the environment-genome interface? Trends Mol Med. 2001 Jan;7(1):13-7. [Article]
  10. Sinko E, Ilias A, Ujhelly O, Homolya L, Scheffer GL, Bergen AA, Sarkadi B, Varadi A: Subcellular localization and N-glycosylation of human ABCC6, expressed in MDCKII cells. Biochem Biophys Res Commun. 2003 Aug 22;308(2):263-9. [Article]
  11. Pomozi V, Le Saux O, Brampton C, Apana A, Ilias A, Szeri F, Martin L, Monostory K, Paku S, Sarkadi B, Szakacs G, Varadi A: ABCC6 is a basolateral plasma membrane protein. Circ Res. 2013 May 24;112(11):e148-51. doi: 10.1161/CIRCRESAHA.111.300194. Epub 2013 Apr 26. [Article]
  12. Ostuni A, Lara P, Armentano MF, Miglionico R, Salvia AM, Monnich M, Carmosino M, Lasorsa FM, Monne M, Nilsson I, Bisaccia F: The hepatitis B x antigen anti-apoptotic effector URG7 is localized to the endoplasmic reticulum membrane. FEBS Lett. 2013 Sep 17;587(18):3058-62. doi: 10.1016/j.febslet.2013.07.042. Epub 2013 Jul 31. [Article]
  13. Germain DP, Perdu J, Remones V, Jeunemaitre X: Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene, is not disease-causing. Biochem Biophys Res Commun. 2000 Aug 2;274(2):297-301. [Article]
  14. Germain DP, Remones V, Perdu J, Jeunemaitre X: Identification of two polymorphisms (c189G>C; c190T>C) in exon 2 of the human MRP6 gene (ABCC6) by screening of Pseudoxanthoma elasticum patients: possible sequence correction? Hum Mutat. 2000 Nov;16(5):449. [Article]
  15. Struk B, Cai L, Zach S, Ji W, Chung J, Lumsden A, Stumm M, Huber M, Schaen L, Kim CA, Goldsmith LA, Viljoen D, Figuera LE, Fuchs W, Munier F, Ramesar R, Hohl D, Richards R, Neldner KH, Lindpaintner K: Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum. J Mol Med (Berl). 2000;78(5):282-6. [Article]
  16. 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. 2000 Jun;25(2):223-7. [Article]
  17. Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J: Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6001-6. [Article]
  18. Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Goring 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. 2001 Oct;69(4):749-64. Epub 2001 Aug 31. [Article]
  19. Pulkkinen L, Nakano A, Ringpfeil F, Uitto J: Identification of ABCC6 pseudogenes on human chromosome 16p: implications for mutation detection in pseudoxanthoma elasticum. Hum Genet. 2001 Sep;109(3):356-65. [Article]
  20. Wang J, Near S, Young K, Connelly PW, Hegele RA: ABCC6 gene polymorphism associated with variation in plasma lipoproteins. J Hum Genet. 2001;46(12):699-705. [Article]
  21. Plomp AS, Hu X, de Jong PT, Bergen AA: Does autosomal dominant pseudoxanthoma elasticum exist? Am J Med Genet A. 2004 May 1;126A(4):403-12. [Article]
  22. Gheduzzi D, Guidetti R, Anzivino C, Tarugi P, Di Leo E, Quaglino D, Ronchetti IP: ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum (PXE). Hum Mutat. 2004 Nov;24(5):438-9. [Article]
  23. Chassaing N, Martin L, Mazereeuw J, Barrie L, Nizard S, Bonafe JL, Calvas P, Hovnanian A: Novel ABCC6 mutations in pseudoxanthoma elasticum. J Invest Dermatol. 2004 Mar;122(3):608-13. [Article]
  24. Miksch S, Lumsden A, Guenther UP, Foernzler D, Christen-Zach S, Daugherty C, Ramesar RK, Lebwohl M, Hohl D, Neldner KH, Lindpaintner K, Richards RI, Struk B: Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. Hum Mutat. 2005 Sep;26(3):235-48. [Article]
  25. Pfendner EG, Vanakker OM, 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. J Med Genet. 2007 Oct;44(10):621-8. Epub 2007 Jul 6. [Article]
  26. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485. [Article]
  27. Ramsay M, Greenberg T, Lombard Z, Labrum R, Lubbe S, Aron S, Marais AS, Terry S, Bercovitch L, Viljoen D: Spectrum of genetic variation at the ABCC6 locus in South Africans: Pseudoxanthoma elasticum patients and healthy individuals. J Dermatol Sci. 2009 Jun;54(3):198-204. doi: 10.1016/j.jdermsci.2009.02.008. Epub 2009 Mar 31. [Article]
  28. Le Boulanger G, Labreze C, Croue A, Schurgers LJ, Chassaing N, Wittkampf T, Rutsch F, Martin L: An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy. Am J Med Genet A. 2010 Jan;152A(1):118-23. doi: 10.1002/ajmg.a.33162. [Article]
  29. Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, Le Merrer M, Guest G, Lambot K, Tazarourte-Pinturier MF, Chassaing N, Roche O, Feenstra I, Loechner K, Deshpande C, Garber SJ, Chikarmane R, Steinmann B, Shahinyan T, Martorell L, Davies J, Smith WE, Kahler SG, McCulloch M, Wraige E, Loidi L, Hohne W, Martin L, Hadj-Rabia S, Terkeltaub R, Rutsch F: Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012 Jan 13;90(1):25-39. doi: 10.1016/j.ajhg.2011.11.020. Epub 2011 Dec 29. [Article]
  30. Jin L, Jiang Q, Wu Z, Shao C, Zhou Y, Yang L, Uitto J, Wang G: Genetic heterogeneity of pseudoxanthoma elasticum: the Chinese signature profile of ABCC6 and ENPP1 mutations. J Invest Dermatol. 2015 May;135(5):1294-302. doi: 10.1038/jid.2015.10. Epub 2015 Jan 23. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01138SulfinpyrazoneapprovedunknowninhibitorDetails
DB01032Probenecidapproved, investigationalunknowninhibitorDetails
DB00328Indomethacinapproved, investigationalunknowninhibitorDetails
DB00773EtoposideapprovedunknownsubstrateinhibitorDetails
DB00997Doxorubicinapproved, investigationalunknownsubstrateinhibitorDetails
DB00570VinblastineapprovedunknowninhibitorDetails
DB00444TeniposideapprovedunknownsubstrateDetails
DB00694DaunorubicinapprovedunknownsubstrateDetails
DB00515CisplatinapprovedunknownsubstrateDetails
DB00970Dactinomycinapproved, investigationalunknownsubstrateDetails
DB00171ATPinvestigational, nutraceuticalunknownDetails