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ATP-binding cassette transporter
ATP-binding cassette transporters (ABC transporters) are members of a transport system superfamily that is one of the largest and is possibly one of the oldest families with representatives in all extant phyla from prokaryotes to humans.
ABC transporters often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membrane-associated ATPases. The ATPase subunits utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to energize the translocation of various substrates across membranes, either for uptake or for export of the substrate.
Most but not all uptake systems also have an extracytoplasmic receptor, a solute binding protein. Some homologous ATPases function in non-transport-related processes such as translation of RNA and DNA repair. ABC transporters are considered to be with the ABC superfamily based on the sequence and organization of their ATP-binding cassette (ABC) domains, even though the integral membrane proteins may have evolved independently several times, and thus comprise different protein families. The integral membrane proteins of ABC exporters appear to have evolved independently at least three times. ABC1 exporters evolved by intragenic triplication of a 2 TMS precursor (TMS= transmembrane segment. a "2 TMS" protein has 2 transmembrane segments) to give 6 TMS proteins. ABC2 exporters evolved by intragenic duplication of a 3 TMS precursor, and ABC3 exporters evolved from a 4 TMS precursor which duplicated either extragenicly to give two 4 TMS proteins, both required for transport function, or intragenicly to give 8 or 10 TMS proteins. The 10 TMS proteins appear to have two extra TMSs between the two 4 TMS repeat units. Like the ABC exporters, it is possible that the integral membrane proteins of ABC uptake systems also evolved at least 3 times independently, based on their high resolution 3-dimensional structures. ABC uptake porters take up a large variety of nutrients, biosynthetic precursors, trace metals and vitamins, while exporters transport lipids, sterols, drugs, and a large variety of primary and secondary metabolites. Some of these exporters in humans are involved in tumor resistance, cystic fibrosis and a range of other inherited human diseases. High level expression of the genes encoding some of these exporters in both prokaryotic and eukaryotic organisms (including human) result in the development of resistance to multiple drugs such as antibiotics and anti-cancer agents.
||This family contains some of the largest transporters (over 2,100 amino acids long). Five of them are located in a cluster in the 17q24 chromosome.
||Responsible for the transportation of cholesterol and lipids, among other things.
||Consists of 4 full and 7 half transporters.
||Some are located in the blood–brain barrier, liver, mitochondria, transports peptides and bile, for example.
||Consists of 12 full transporters.
||Used in ion transport, cell-surface receptors, toxin secretion. Includes the CFTR protein, which causes cystic fibrosis when deficient.
||Consists of 4 half transporters
||Are all used in peroxisomes.
||Consists of 1 ABCE and 3 ABCF proteins.
||These are not actually transporters but merely ATP-binding domains that were derived from the ABC family, but without the transmembrane domains. These proteins mainly regulate protein synthesis or expression.
||ABCE, ABCF1, ABCF2
||Consists of 6 "reverse" half-transporters, with the NBF at the NH3+ end and the TM at the COO- end.
||Transports lipids, diverse drug substrates, bile, cholesterol, and other steroids.
- 3.A.1.1 Carbohydrate Uptake Transporter-1 (CUT1)
- 3.A.1.2 Carbohydrate Uptake Transporter-2 (CUT2)
- 3.A.1.3 Polar Amino Acid Uptake Transporter (PAAT)
- 3.A.1.4 Hydrophobic Amino Acid Uptake Transporter (HAAT)
- 3.A.1.5 Peptide/Opine/Nickel Uptake Transporter (PepT)
- 3.A.1.6 Sulfate/Tungstate Uptake Transporter (SulT)
- 3.A.1.7 Phosphate Uptake Transporter (PhoT)
- 3.A.1.8 Molybdate Uptake Transporter (MolT)
- 3.A.1.9 Phosphonate Uptake Transporter (PhnT)
- 3.A.1.10 Ferric Iron Uptake Transporter (FeT)
- 3.A.1.11 Polyamine/Opine/Phosphonate Uptake Transporter (POPT)
- 3.A.1.12 Quaternary Amine Uptake Transporter (QAT)
- 3.A.1.13 Vitamin B12 Uptake Transporter (B12T)
- 3.A.1.14 Iron Chelate Uptake Transporter (FeCT)
- 3.A.1.15 Manganese/Zinc/Iron Chelate Uptake Transporter (MZT)
- 3.A.1.16 Nitrate/Nitrite/Cyanate Uptake Transporter (NitT)
- 3.A.1.17 Taurine Uptake Transporter (TauT)
- 3.A.1.18 Cobalt Uptake Transporter (CoT)
- 3.A.1.19 Thiamin Uptake Transporter (ThiT)
- 3.A.1.20 Brachyspira Iron Transporter (BIT)
- Siderophore-Fe3+ Uptake Transporter (SIUT)
- Nickel Uptake Transporter (NiT)
- Methionine Uptake Transporter (MUT)
- 2.A.52 Nickel/Cobalt Uptake Transporter (NiCoT)
- 3.A.1.106 Lipid Exporter (LipidE)
- 3.A.1.101 Capsular polysaccharide exporter (CPSE) family
- 3.A.1.102 Lipooligosaccharide exporter (LOSE) family
- 3.A.1.103 Lipopolysaccharide exporter (LPSE) family
- 3.A.1.104 Teichoic acid exporter (TAE) family
- 3.A.1.105 Drug exporter (DrugE1) family
- 3.A.1.106 Putative lipid A exporter (LipidE) family
- 3.A.1.107 Putative heme exporter (HemeE) family
- 3.A.1.108 β-Glucan exporter (GlucanE) family
- 3.A.1.109 Protein-1 exporter (Prot1E) family
- 3.A.1.110 Protein-2 exporter (Prot2E) family
- 3.A.1.111 Peptide-1 exporter (Pep1E) family
- 3.A.1.112 Peptide-2 exporter (Pep2E) family
- 3.A.1.113 Peptide-3 exporter (Pep3E) family
- 3.A.1.114 Probable glycolipid exporter (DevE) family
- 3.A.1.115 Na+ exporter (NatE) family
- 3.A.1.116 Microcin B17 exporter (McbE) family
- 3.A.1.117 Drug exporter-2 (DrugE2) family
- 3.A.1.118 Microcin J25 exporter (McjD) family
- 3.A.1.119 Drug/siderophore exporter-3 (DrugE3) family
- (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 and glutathione Exporter (CydDC-E)
- 3.A.1.106 The Lipid Exporter (LipidE) Family
- 3.A.1.108 The β-Glucan Exporter (GlucanE) Family
- 3.A.1.109 The Protein-1 Exporter (Prot1E) Family
- 3.A.1.110 The Protein-2 Exporter (Prot2E) Family
- 3.A.1.111 The Peptide-1 Exporter (Pep1E) Family
- 3.A.1.112 The Peptide-2 Exporter (Pep2E) Family
- 3.A.1.113 The Peptide-3 Exporter (Pep3E) Family
- 3.A.1.117 The Drug Exporter-2 (DrugE2) Family
- 3.A.1.118 The Microcin J25 Exporter (McjD) Family
- 3.A.1.119 The Drug/Siderophore Exporter-3 (DrugE3) Family
- 3.A.1.123 The Peptide-4 Exporter (Pep4E) Family
- 3.A.1.127 The AmfS Peptide Exporter (AmfS-E) Family
- 3.A.1.129 The CydDC Cysteine Exporter (CydDC-E) Family
- 3.A.1.135 The Drug Exporter-4 (DrugE4) Family
- 3.A.1.139 The UDP-Glucose Exporter (U-GlcE) Family (UPF0014 Family)
- 3.A.1.201 The Multidrug Resistance Exporter (MDR) Family (ABCB)
- 3.A.1.202 The Cystic Fibrosis Transmembrane Conductance Exporter (CFTR) Family (ABCC)
- 3.A.1.203 The Peroxysomal Fatty Acyl CoA Transporter (P-FAT) Family (ABCD)
- 3.A.1.206 The a-Factor Sex Pheromone Exporter (STE) Family (ABCB)
- 3.A.1.208 The Drug Conjugate Transporter (DCT) Family (ABCC) (Dębska et al., 2011)
- 3.A.1.209 The MHC Peptide Transporter (TAP) Family (ABCB)
- 3.A.1.210 The Heavy Metal Transporter (HMT) Family (ABCB)
- 3.A.1.212 The Mitochondrial Peptide Exporter (MPE) Family (ABCB)
- 3.A.1.21 The Siderophore-Fe3+ Uptake Transporter (SIUT) Family
- 3.A.1.101 The Capsular Polysaccharide Exporter (CPSE) Family
- 3.A.1.102 The Lipooligosaccharide Exporter (LOSE) Family
- 3.A.1.103 The Lipopolysaccharide Exporter (LPSE) Family
- 3.A.1.104 The Teichoic Acid Exporter (TAE) Family
- 3.A.1.105 The Drug Exporter-1 (DrugE1) Family
- 3.A.1.107 The Putative Heme Exporter (HemeE) Family
- 3.A.1.115 The Na+ Exporter (NatE) Family
- 3.A.1.116 The Microcin B17 Exporter (McbE) Family
- 3.A.1.124 The 3-component Peptide-5 Exporter (Pep5E) Family
- 3.A.1.126 The β-Exotoxin I Exporter (βETE) Family
- 3.A.1.128 The SkfA Peptide Exporter (SkfA-E) Family
- 3.A.1.130 The Multidrug/Hemolysin Exporter (MHE) Family
- 3.A.1.131 The Bacitracin Resistance (Bcr) Family
- 3.A.1.132 The Gliding Motility ABC Transporter (Gld) Family
- 3.A.1.133 The Peptide-6 Exporter (Pep6E) Family
- 3.A.1.138 The Unknown ABC-2-type (ABC2-1) Family
- 3.A.1.141 The Ethyl Viologen Exporter (EVE) Family (DUF990 Family)
- 3.A.1.142 The Glycolipid Flippase (G.L.Flippase) Family
- 3.A.1.143 The Exoprotein Secretion System (EcsAB(C))
- 3.A.1.204 The Eye Pigment Precursor Transporter (EPP) Family (ABCG)
- 3.A.1.205 The Pleiotropic Drug Resistance (PDR) Family (ABCG)
- 3.A.1.211 The Cholesterol/Phospholipid/Retinal (CPR) Flippase Family (ABCA)
- 9.B.74 The Phage Infection Protein (PIP) Family
- 3.A.1.114 The Probable Glycolipid Exporter (DevE) Family
- 3.A.1.122 The Macrolide Exporter (MacB) Family
- 3.A.1.125 The Lipoprotein Translocase (LPT) Family
- 3.A.1.134 The Peptide-7 Exporter (Pep7E) Family
- 3.A.1.136 The Uncharacterized ABC-3-type (U-ABC3-1) Family
- 3.A.1.137 The Uncharacterized ABC-3-type (U-ABC3-2) Family
- 3.A.1.140 The FtsX/FtsE Septation (FtsX/FtsE) Family
- 3.A.1.207 The Eukaryotic ABC3 (E-ABC3) Family
- 3.A.1.18 The Cobalt Uptake Transporter (CoT) Family
- 3.A.1.22 The Nickel Uptake Transporter (NiT) Family
- 3.A.1.23 The Nickel/Cobalt Uptake Transporter (NiCoT) Family
- 3.A.1.25 The Biotin Uptake Transporter (BioMNY) Family
- 3.A.1.26 The Putative Thiamine Uptake Transporter (ThiW) Family
- 3.A.1.28 The Queuosine (Queuosine) Family
- 3.A.1.29 The Methionine Precursor (Met-P) Family
- 3.A.1.30 The Thiamin Precursor (Thi-P) Family
- 3.A.1.31 The Unknown-ABC1 (U-ABC1) Family
- 3.A.1.32 The Cobalamin Precursor (B12-P) Family
- 3.A.1.33 The Methylthioadenosine (MTA) Family
- 2.A.87 The Prokaryotic Riboflavin Transporter (P-RFT) Family
- 2.A.88 The Vitamin Uptake Transporter (VUT or ECF) Family
Szentpétery Z, Kern A, Liliom K, Sarkadi B, Váradi A, Bakos E (Oct 2004). "The role of the conserved glycines of ATP-binding cassette signature motifs of MRP1 in the communication between the substrate-binding site and the catalytic centers". The Journal of Biological Chemistry. 279 (40): 41670–8. doi:10.1074/jbc.M406484200. PMID 15252017.
Fitzgerald ML, Okuhira K, Short GF, Manning JJ, Bell SA, Freeman MW (Nov 2004). "ATP-binding cassette transporter A1 contains a novel C-terminal VFVNFA motif that is required for its cholesterol efflux and ApoA-I binding activities". The Journal of Biological Chemistry. 279 (46): 48477–85. doi:10.1074/jbc.M409848200. PMID 15347662.
Linton KJ (2011). The ABC Transporters of Human Physiology and Disease: The Genetics and Biochemistry of ATP Binding Cassette. World Scientific Publishing Company. ISBN .
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