ATP-binding cassette transporter genes

ATP-binding cassette transporter genes (ABC-transporter genes) are a superfamily of genes which encode the ABC-transporter proteins. These are transmembrane proteins that function in the transport of a wide variety of substrates across extra- and intracellular membranes, including metabolic products, lipids and sterols, and drugs. Proteins are classified as ABC transporters based on the sequence and organization of their ATP-binding domain(s), also known as nucleotide-binding folds (NBFs). The NBFs contain characteristic motifs, called Walker A and B, separated by approximately 90 --120 amino acids, found in all ATP-binding proteins. ABC genes also contain an additional element, the signature (C) motif, located just upstream of the Walker B site

ABC-transporter proteins

The ABC-transporter protein superfamily is one of the largest and most ancient families with representatives in all extant phyla. They are transmembrane proteins characterized by an "ATP-binding Cassette" protein motif. ABC-transporter proteins span the membrane multiple times.

Function

ABC-transporter proteins utilize the energy of ATP hydrolysis to transport of a wide variety of substrates across extra- and intracellular membranes, including:

Lipids and sterols;
Ions and small molecules.
Drugs;
Large polypeptides.

Structure

ABC-transporter proteins are multidomain integral membrane proteins characterized by an "ATP-binding Cassette" protein motif, which is a short, highly conserved polypeptide motif located between a Walker motif A and a Walker motif B of the ABC-transporter protein.

Images

A wealth of high-resolution structures of ABC proteins have been produced in recent years.

Subfamilies

Eukaryotic Subfamilies

ABCA
- Cholesterol/Phospholipid/Retinal (CPR) Flippase - ABC1
ABCB
- Multidrug Resistance Exporter (MDR) - ABCB1
- MHC Peptide Transporter (TAP)
- a-Factor Sex Pheromone Exporter (STE)
- Heavy Metal Transporter (HMT) Family
- Mitochondrial Peptide Exporter (MPE)
ABCC
- CFTR Cystic Fibrosis Transmembrane Conductance Regulator - ABCC7
- MRP Multidrug Resistance Protein
- Conjugate Transporter - ABCC6
ABCD
- Peroxysomal Fatty Acyl CoA Transporter (P-FAT)(ALD)
ABCE
- OABP
ABCF
- GCN20
ABCG
- Eye Pigment Precursor Transporter (EPP) - WHITE
- Pleiotropic Drug Resistance (PDR)

Prokaryotic Subfamilies

Importer

Carbohydrate Uptake Transporter-1 (CUT1)
Carbohydrate Uptake Transporter-2 (CUT2)
Polar Amino Acid Uptake Transporter (PAAT)
Peptide/Opine/Nickel Uptake Transporter (PepT)
Hydrophobic Amino Acid Uptake Transporter (HAAT)
Sulfate/Tungstate Uptake Transporter (SulT)
Phosphate Uptake Transporter (PhoT)
Molybdate Uptake Transporter (MolT)
Phosphonate Uptake Transporter (PhnT)
Ferric Iron Uptake Transporter (FeT)
Polyamine/Opine/Phosphonate Uptake Transporter (POPT)
Quaternary Amine Uptake Transporter (QAT)
Vitamin B12 Uptake Transporter (B12T)
Iron Chelate Uptake Transporter (FeCT)
Manganese/Zinc/Iron Chelate Uptake Transporter (MZT)
Nitrate/Nitrite/Cyanate Uptake Transporter (NitT)
Taurine Uptake Transporter (TauT)
Cobalt Uptake Transporter (CoT)
Thiamin Uptake Transporter (ThiT)
Brachyspira Iron Transporter (BIT)
Siderophore-Fe3+ Uptake Transporter (SIUT)
Nickel Uptake Transporter (NiT)
Nickel/Cobalt Uptake Transporter (NiCoT)
Methionine Uptake Transporter (MUT)
Lipid Exporter (LipidE)

Exporter

Capsular Polysaccharide Exporter (CPSE)
Lipooligosaccharide Exporter (LOSE)
Lipopolysaccharide Exporter (LPSE)
Teichoic Acid Exporter (TAE)
Drug Exporter-1 (DrugE1)
Lipid Exporter (LipidE)
Putative Heme Exporter (HemeE)
β-Glucan Exporter (GlucanE)
Protein-1 Exporter (Prot1E)
Protein-2 Exporter (Prot2E)
Peptide-1 Exporter (Pep1E)
Peptide-2 Exporter (Pep2E)
Peptide-3 Exporter (Pep3E)
Probable Glycolipid Exporter (DevE)
Na+ Exporter (NatE)
Microcin B17 Exporter (McbE)
Drug Exporter-2 (DrugE2)
Microcin J25 Exporter (McjD)
Drug/Siderophore Exporter-3 (DrugE3)
(Putative) Drug Resistance ATPase-1 (Drug RA1)
(Putative) Drug Resistance ATPase-2 (Drug RA2)
Macrolide Exporter (MacB)
Peptide-4 Exporter (Pep4E)
3-component Peptide-5 Exporter (Pep5E)
Lipoprotein Translocase (LPT)
β-Exotoxin I Exporter (βETE)
AmfS Peptide Exporter (AmfS-E)
SkfA Peptide Exporter (SkfA-E)
CydDC Cysteine Exporter (CydDC-E)

Host organisms

ABC-transporter genes are found in all model organisms from prokaryotes to humans; representatives have been found all extant phyla. In humans, this family is thought to comprise at least 49 members, 13 of which belong to the ABCA class of transporters.

Human disorders involving ABC-transporter genes

Cancer cell lines.
Multidrug resistant tumors.
Cystic fibrosis;
Neurological disease;
Retinal degeneration;
Cholesterol and bile transport defects;
Anemia;
Drug response phenotypes;
Resistance of pathogenic microbes to drugs;
Congenital bilateral absence of vas deferens;
Congenital hyperinsulinemia;
Stargardt’s disease;
Hyperbilirubinemia;
Tangier disease;

Examples

ABCB 6-8 and 10 family members provide an example of the functions of member of the family; These proteins transport iron across the inner mitochondrial membrane for usage in synthesis of heme, disruption of which transport can result in anemia.

History

ATP-binding cassette transporter genes were first identified over thirty years ago in prokaryotes, but have only relatively recently been isolated in humans. One of the first human ABC genes to be characterised was CFTR (ABCC), since which time a further 37 genes have been identified.

References

Jones, P. M.; George, A. M.; Cellular and Molecular Life Sciences. 2004, 61, 682-699.
Dean, Michael. The Human ATP-Binding Cassette (ABC) Transporter Superfamily. Bethesda (MD):National Library of Medicine (US), NCBI; 2002 November.
Szentpétery, Z.; Kern, A.; Liliom, K.; Sarkadi, B.; Váradi, A.; Bakos, E.; J. Biol. Chem. 2004, 279, 41670-41678. ^*
ABC Nomenclature Committee. ABC-Transporter Genes nomenclature scheme, enacted October 22, 1999. Verified availability August 2, 2005.
Fitzgerald, M. L.; Okuhira, K.; Short, G. F.; Manning, J. J.; Bell, S. A.; Freeman, M. W.; J. Biol. Chem. 2004, 279, 48477-48485.
Wain, H. M.; White, J. A.; Povey, S. ^*
Saier MH Jr.; Microbiol Mol Biol Rev., 2000, 64(2), 354-411 TCDB
Deeley, R. G. ^*

Membrane biology

Gourt Home::Gourt :: ATP-binding cassette transporter genes