Home LiteratureArticle Details
PMID: 11804186 Published · ppublish English Journal Article Review

Overview: ABC transporters and human disease.

Journal of bioenergetics and biomembranes ·Vol. 33 ·No. 6 ·2001-12-00 ·Pages 453-8

Gottesman MM, Ambudkar SV

Abstract

ABC transporters are found in all known organisms, and approximately 1,100 different transporters belonging to this family have been described in the literature. The family is defined by homology within the ATP-binding cassette (ABC) region, which extends outside of the more typical Walker motifs found in all ATP-binding proteins. Most family members also contain transmembrane domains involved in recognition of substrates, which are transported across, into, and out of cell membranes, but some members utilize ABCs as engines to regulate ion channels. There are approximately 50 known ABC transporters in the human, and there are currently 13 genetic diseases associated with defects in 14 of these transporters. The most common genetic disease conditions include cystic fibrosis, Stargardt disease, age-related macular degeneration, adrenoleukodystrophy, Tangier disease, Dubin-Johnson syndrome and progressive familial intrahepatic cholestasis. At least 8 members of this family are involved in the transport of a variety of amphipathic compounds, including anticancer drugs, and some appear to contribute to the resistance of cancer cells to chemotherapy.

MeSH Terms
ATP-Binding Cassette Transporters/genetics,physiology Amino Acid Sequence Drug Resistance, Multiple Genetic Diseases, Inborn/genetics,physiopathology Humans Immune System Diseases/genetics,physiopathology Molecular Sequence Data Neoplasms/genetics,physiopathology
Chemicals
ATP-Binding Cassette Transporters
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gottesman M M
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. mgottesman@nih.gov
Ambudkar S V
References (41)
41 references, click to expand
  1. Peroxisomal ABC transporters.
    Methods Enzymol. 1998;292:753-76 PMID: 9711597
  2. Selectivity of MHC-encoded peptide transporters from human, mouse and rat.
    Nature. 1994 Feb 17;367 (6464):648-51 PMID: 8107849
  3. Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking.
    Hum Mol Genet. 2000 May 1;9(8):1209-17 PMID: 10767346
  4. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.
    Science. 2000 Dec 1;290(5497):1771-5 PMID: 11099417
  5. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance.
    Cancer Res. 1998 Dec 1;58(23):5337-9 PMID: 9850061
  6. Structure-function analysis of hemolysin B.
    Methods Enzymol. 1998;292:51-66 PMID: 9711546
  7. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
    Science. 1989 Sep 8;245(4922):1066-73 PMID: 2475911
  8. Crystal structure of the ATP-binding subunit of an ABC transporter.
    Nature. 1998 Dec 17;396(6712):703-7 PMID: 9872322
  9. The pharmacological phenotype of combined multidrug-resistance mdr1a/1b- and mrp1-deficient mice.
    Cancer Res. 2001 Feb 15;61(4):1469-76 PMID: 11245453
  10. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis.
    Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):282-7 PMID: 9419367
  11. Genetic basis of sitosterolemia.
    Curr Opin Lipidol. 2001 Apr;12(2):141-9 PMID: 11264985
  12. Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA.
    Nature. 2000 Oct 12;407(6805):703-10 PMID: 11048710
  13. Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome.
    Hum Mol Genet. 1998 Feb;7(2):203-7 PMID: 9425227
  14. Extensive contribution of the multidrug transporters P-glycoprotein and Mrp1 to basal drug resistance.
    Cancer Res. 2000 Oct 15;60(20):5761-6 PMID: 11059771
  15. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.
    Nat Genet. 1998 Nov;20(3):233-8 PMID: 9806540
  16. Biochemistry of multidrug resistance mediated by the multidrug transporter.
    Annu Rev Biochem. 1993;62:385-427 PMID: 8102521
  17. Biochemical, cellular, and pharmacological aspects of the multidrug transporter.
    Annu Rev Pharmacol Toxicol. 1999;39:361-98 PMID: 10331089
  18. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency.
    Nat Genet. 1999 Aug;22(4):336-45 PMID: 10431236
  19. Characterization of the catalytic cycle of ATP hydrolysis by human P-glycoprotein. The two ATP hydrolysis events in a single catalytic cycle are kinetically similar but affect different functional outcomes.
    J Biol Chem. 2001 Apr 13;276(15):11653-61 PMID: 11154703
  20. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1.
    Nat Genet. 1999 Aug;22(4):352-5 PMID: 10431238
  21. Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein.
    Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2515-20 PMID: 10716986
  22. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene.
    Science. 1996 Feb 23;271(5252):1126-8 PMID: 8599091
  23. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3473-8 PMID: 10716719
  24. Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease.
    J Biol Chem. 1999 Mar 19;274(12):8269-81 PMID: 10075733
  25. The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch.
    Nature. 2000 Oct 12;407(6805):711-7 PMID: 11048711
  26. Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter.
    Nature. 1991 Dec 19-26;354(6354):528-31 PMID: 1758495
  27. ABC transporters: from microorganisms to man.
    Annu Rev Cell Biol. 1992;8:67-113 PMID: 1282354
  28. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.
    Science. 1995 Apr 21;268(5209):426-9 PMID: 7716548
  29. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells.
    Cell. 1986 Nov 7;47(3):381-9 PMID: 2876781
  30. Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene.
    J Pharmacol Exp Ther. 2001 Jun;297(3):1137-43 PMID: 11356939
  31. Translation elongation factor-3 (EF-3): an evolving eukaryotic ribosomal protein?
    J Mol Evol. 1995 Sep;41(3):376-87 PMID: 7563124
  32. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.
    Science. 1992 Dec 4;258(5088):1650-4 PMID: 1360704
  33. Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter of the archaeon Thermococcus litoralis.
    EMBO J. 2000 Nov 15;19(22):5951-61 PMID: 11080142
  34. Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A).
    Hum Mol Genet. 1999 May;8(5):743-9 PMID: 10196363
  35. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4028-33 PMID: 9108099
  36. Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes.
    Cancer Res. 1999 Jan 1;59(1):8-13 PMID: 9892175
  37. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy.
    Nat Genet. 1997 Mar;15(3):236-46 PMID: 9054934
  38. Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter.
    Structure. 2001 Jul 3;9(7):571-86 PMID: 11470432
  39. Sulfonylurea receptors: ABC transporters that regulate ATP-sensitive K(+) channels.
    Biochim Biophys Acta. 1999 Dec 6;1461(2):285-303 PMID: 10581362
  40. 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 PMID: 10811882
  41. Structure of the ArsA ATPase: the catalytic subunit of a heavy metal resistance pump.
    EMBO J. 2000 Sep 1;19(17):4838-45 PMID: 10970874
Article Info
Journal
Journal of bioenergetics and biomembranes
Abbr.
J Bioenerg Biomembr
ISSN
0145-479X
Published
2001-12-00
Pages
453-8
Language
English
Region
United States
NLM ID
7701859
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com