3.A.1 The ATP-binding Cassette (ABC) Superfamily

The ABC superfamily contains both uptake and efflux transport systems, and the members of these two porter groups generally cluster loosely together with just a few exceptions. ATP hydrolysis without protein phosphorylation energizes transport. There are dozens of families within the ABC superfamily, and family generally correlates with substrate specificity. However there are exceptions.

The porters of the ABC superfamily consist of two integral membrane domains/proteins and two cytoplasmic domains/proteins. The uptake systems (but not the efflux systems) additionally possess extracytoplasmic solute-binding receptors (one or more per system) which in Gram-negative bacteria is found in the periplasm, and in Gram-positive bacteria is present either as a lipoprotein, tethered to the external surface of the cytoplasmic membrane, or as a cell surface-associated protein, bound to the external membrane surface via electrostatic interactions. For those systems with two or more extracytoplasmic solute binding receptors, the receptors may interact in a cooperative fashion (Biemans-Oldehinkel and Poolman, 2003). Both the integral membrane channel constituent(s) and the cytoplasmic ATP-hydrolyzing constituent(s) may be present as homodimers or heterodimers. Two families of ABC transporters have members in which one or two receptors are fused to either the N- or C-terminus of the translocating membrane protein. This suggests that two or even four substrate-binding sites may function in the complex. Possibly multiple receptors in proximity to the translocator enhances the transport rate. Multiple receptors may also broaden the substrate specificity of the system (van der Heide and Poolman, 2002). These systems with covalent receptor domains linked to the transmembrane translocators are found in the PAAT family (TC #3.A.1.3) and the QAT family (TC #3.A.1.12) (van der Heide and Poolman, 2002).

The homodimeric LmrA drug efflux pump (TC #3.A.1.117.1) of Lactococcus lactis appears to function by an alternating site (half of sites) type mechanism. In many of these porters, the various domains are fused in a variety of combinations. Uptake porters generally have their constituents as distinct polypeptide chains, while efflux systems usually have them fused. ABC-type uptake systems have not been identified in eukaryotes, but ABC-type efflux systems abound in both prokaryotes and eukaryotes. The eukaryotic efflux systems often have the four domains (two cytoplasmic domains and two integral membrane domains) fused into either one or two polypeptide chains. The integral membrane porter domains each usually possesses 5 (uptake) or 6 (efflux) transmembrane spanners, but exceptions exist. For example, the MntB protein (TC #3.A.1.15.1) exhibits 9 established TMSs. The 3-dimensional structure of the E. coli MsbA protein (TC #3.A.1.106.1) has been solved to a resolution of 4.5 Å (Chang and Roth, 2001), and that of the E. coli BtuCD Vitamin B12 transporter was solved at 3.2 Å resolution (Locher et al., 2002). The two structures are very different, but the two transmembrane domains form a single barrel 5-6 nm in diameter and about 5 nm deep with a entral pore open to the external surface spanning much of the membrane (Rosenberg et al., 2003). A model has been proposed allowing the channel to open up to the lipid bilayer. A half of sites model in which the two nucleotide binding domains interact in a fashion controlled by substrate binding has also been proposed (Hou et al., 2003; Loo et al., 2003).

The three structurally dissimilar constituents of the ABC uptake porters have generally arisen from a common ancestral porter system with minimal shuffling of constituents between systems. Thus, phylogenetic clustering of the three protein/domain constituents is almost always the same. However the rates of sequence divergences differ drastically with the extracytoplasmic solute-binding receptors diverging most rapidly, the integral-membrane, channel-forming constituents diverging at an intermediate rate, and the cytoplasmic ATP-hydrolyzing constituents diverging most slowly. Thus, all ATP-hydrolyzing constituents are demonstrably homologous, but this is not true for the integral membrane constituents or the receptors. Nevertheless, clustering patterns are generally the same for all three types of proteins, and 3-dimensional structural data suggest that, in spite of their extensive sequence divergence, the extracytoplasmic solute-binding receptors are homologous to each other.

Dassa and Bouige (2001) have recently devised a phylogenetic/functional classification system for ABC transporters that overlaps the TC system. In their system, several of the TC families are included in single families. These reveal the closer phylogenetic relationship of TC families as follows:

Table 1
D&B Family	TC Families
Uptake
MOI	SulT, + PhoT + MolT + FeT + POPT + ThiT
OTCN	QAT + NitT + TauT
ISVH	VB12 + FeCT
Export
DPL	Lipid E + Glucan E + Prot1E + Prot2E + Pep1E + Pep2E + Pep3E + DrugE2 + DrugE3 + MDR + CFTR + Ste + TAP + HMT + MPE
OAD	CT1 + CT2
EPD	EPP + PDR
DRA	DrugE1 + CPR
DRI	NatE
CLS	CPSE + LPSE + TAE

Dassa and Bouige (2001) also provide the protein and domain organization of each of the various family-type proteins (see Table 1).

The generalized transport reaction for ABC-type uptake systems is:

Solute (out) + ATP → Solute (in) + ADP + P_i.

The generalized transport reaction for ABC-type efflux systems is:

Substrate (in) + ATP → Substrate (out) + ADP + P_i.

REFERENCES:

ABC-type Uptake Porters (All from Prokaryotes (Bacteria and Archaea))

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Bartsevich, V.V. and H.B. Pakrasi. (1999). Membrane topology of MntB, the transmembrane protein component of an ABC transporter system for manganese in the cyanobacterium Synechocystis sp. strain PCC6803. J. Bacteriol. 181: 3591-3593.

Bearden, S.W. and R.D. Perry. (1999). The Yfe system of Yersinia pestis transports iron and manganese and is required for full virulence of plague. Mol. Microbiol. 32: 403-414.

Beckers, G., A.K. Bendt, R. Kramer, and A. Burkovski. (2004). Molecular identification of the urea uptake system and transcriptional analysis of urea transporter- and urease-encoding genes in Corynebacterium glutamicum. J. Bacteriol. 186: 7645-7652.

Biemans-Oldehinkel, E. and B. Poolman. (2003). On the role of the two extracytoplasmic substrate-binding domains in the ABC transporter OpuA. EMBO J. 22: 5983-5993.

Börnke, F., M. Hajirezaei, and U. Sonnewald. (2001). Cloning and characterization of the gene cluster for palatinose metabolism from the phytopathogenic bacterium Erwinia rhapontici. J. Bacteriol. 183: 2425-2430.

Bossé, J.T., H.D. Gilmour, and J.I. MacInnes. (2001). Novel genes affecting urease activity in Actinobacillus pleuropneumoniae. J. Bacteriol. 183: 1242-1247.

Braibant, M., P. Gilot, and J. Content. (2000). The ATP binding cassette (ABC) transport systems of Mycobacterium tuberculosis. FEMS Microbiol. Rev. 24: 449-467.

Burguière, P., S. Auger, M.-F. Hullo, A. Danchin, and I. Martin-Verstraete. (2004). Three different systems particpate in L-cystine uptake in Bacillus subtilis. J. Bacteriol. 186: 4875-4884.

Chen, Y.-Y.M. and R.A. Burne. (2003). Identification and characterization of the nickel uptake system for urease biogenesis in Streptococcus salivarius 57.I. J. Bacteriol. 185: 6773-6779.

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De Costa, D.M., K. Suzuki, and K. Yoshida. (2003). Structural and functional analysis of a putative gene cluster for palatinose transport on the linear chromosome of Agrobacterium tumefaciens MAFF301001. J. Bacteriol. 185: 2369-2373.

Diederichs, K., J. Diez, G. Greller, C. Müller, J. Breed, C. Schnell, C. Vonrhein, W. Boos, and W. Welte. (2000). Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter of the archaeon Thermococcus litoralis. EMBO J. 19: 5951-5961.

Dintilhac, A., G. Alloing, C. Granadel, and J.-P. Claverys. (1997). Competence and virulence of Streptococcus pneumoniae: Adc and PsaA mutants exhibit a requirement for Zn and Mn resulting from inactivation of putative ABC metal permeases. Mol. Microbiol. 25: 727-739.

Doeven, M.K., R. Abele, R. Tampé, and B. Poolman. (2004). The binding specificity of OppA determines the selectivity of the oligopeptide ATP-binding cassette transporter. J. Biol. Chem. 279: 32301-32307.

Dugourd, D., C. Martin, C.R. Rioux, M.Jacques, and J. Harel. (1999). Charecterization of a periplasmic ATP-binding cassette iron import system of Brachyspira (serpulina) hyodysenteriae. J. Bacteriol. 181: 6948-6957.

Dupont, L., I. Garcia, M.-C. Poggi, G. Alloing, K. Mandon, and D. Le Rudulier. (2004). The Sinorhizobium meliloti ABC transporter Cho is highly specific for choline and expressed in bacteroids from Medicago sativa nodules. J. Bacteriol. 186: 5988-5996.

Elferink, M.G.L., S.-V. Albers, W.N. Konings, and A.J.M. Driessen. (2001). Sugar transport in Sulfolobus solfataricus is mediated by two families of binding protein-dependent ABC transporters. Mol. Microbiol. 39: 1494-1503.

Fetherston, J.D., V.J. Bertolino, and R.D. Perry. (1999). YbtP and YbtQ: two ABC transporters required for iron uptake in Yersinia pestis. Mol. Microbiol. 32: 289-299.

Fiedler, G., M. Pajatsch, and A. Böck. (1996). Genetics of a novel starch utilisation pathway present in Klebsiella oxytoca. J. Mol. Biol. 256: 279-291.

Hazlett, K.R.O., F. Rusnak, D.G. Kehres, S.W. Bearden, C.J. La Vake, M.E. La Vake, M.E. Maguire, R.D. Perry, and J.D. Radolf. (2003). The Treponema pallidum tro operon encodes a multiple metal transporter, a zinc-dependent transcriptional repressor, and a semi-autonomously expressed phosphoglycerate mutase. J. Biol. Chem. 278: 20687-20694.

Holland, I.B., S.P.C. Cole, K. Kuchler, and C.F. Higgins (Eds.). (2003). ABC Proteins: From Bacteria to Man. London: Academic Press/Elsevier Science.

Horlacher, R., K.B. Xavier, H. Santos, J. DiRuggiero, M. Kossmann, and W. Boos. (1998). Archeal binding protein-dependent ABC transporter: molecular and biochemical analysis of the trehalose/maltose transport system of the hyperthermophilic archaeon Thermococcus litoralis. J. Bacteriol. 180: 680-689.

Hosie, A.H.F., D. Allaway, C.S. Galloway, H.A. Dunsby, and P.S. Poole. (2002). Rhizobium leguminosarum has a second general amino acid permease with unusually broad substrate specificity and high similarity to branched-chain amino acid transporters (Bra/LIV) of the ABC family. J. Bacteriol. 184: 4071-4080.

Hugouvieux-Cotte-Pattat, N. and S. Reverchon. (2001). Two transporters, TogT and TogMNAB, are responsible for oligogalacturonide uptake in Erwinia chrysanthemi 3937. Mol. Microbiol. 41: 1125-1132.

Hullo, M.F., S. Auger, E. Dassa, A. Danchin, and I. Martin-Verstraete. (2004). The metNPQ operon of Bacillus subtilis encodes an ABC permease transporting methionine sulfoxide, d- and l-methionine. Res. Microbiol. 155: 80-86.

Jensen, J.B., N.K. Peters, and T.V. Bhuvaneswari. (2002). Redundancy in periplasmic binding protein-dependent transport systems for trehalose, sucrose, and maltose in Sinorhizobium meliloti. J. Bacteriol. 184: 2978-2986.

Kahnert, A., P. Vermeij, C. Wietek, P. James, T. Leisinger, and M.S. Kertesz. (2000). The ssu locus plays a key role in organosulfur metabolism in Pseudomonas putida S-313. J. Bacteriol. 182: 2869-2878.

Kappes, R.M. and E. Bremer. (1998). Response of Bacillus subtilis to high osmolarity: uptake of carnitine, crotonobetaine and γ-butyrobetaine via the ABC transport system OpuC. Microbiology 144: 83-90.

Kashiwagi, K., M.H. Tsuhako, K. Sakata, T. Saisho, A. Igarashi, S.O.P. da Costa, and K. Igarashi. (1998). Relationship between spontaneous aminoglycoside resistance in Escherichia coli and a decrease in oligopeptide binding protein. J. Bacteriol. 180: 5485-5488.

Kehres, D.G., A. Janakiraman, J.M. Slauch, and M.E. Maguire. (2002). SitABCD is the alkaline Mn²⁺ transporter of Salmonella enterica serovar typhimurium. J. Bacteriol. 184: 3159-3166.

Kempf, B. and E. Bremer. (1998). Uptake and synthesis of compatible solutes as microbial stress responses to high-osmolality environments. Arch. Microbiol. 170: 319-330.

Kim, C., S. Song, and C. Park. (1997). The D-allose operon of Escherichia coli K-12. J. Bacteriol. 179: 7631-7637.

King, N.D. and M.R. O'Brian. (2001). Evidence for direct interaction between Enzyme I^Ntr and aspartokinase to regulate bacterial oligopeptide transport. J. Biol. Chem. 276: 21311-21316.

Kolenbrander, P.E., R.N. Andersen, R.A. Baker, and H.F. Jenkinson. (1998). The adhesion-associated sca operon in Streptococcus gordonii encodes an inducible high-affinity ABC transporter for Mn²⁺ uptake. J. Bacteriol. 180: 290-295.

Koyanagi, T., T. Katayama, H. Suzuki, and H. Kumagai. (2004). Identification of the LIV-I/LS system as a third phenylalanine transporter in Escherichia coli K-12. J. Bacteriol. 186: 343-350.

Kuan, G., E. Dassa, W. Saurin, M. Hofnung, and M.H. Saier, Jr. (1995). Phylogenetic analyses of the ATP-binding constituents of bacterial extracytoplasmic receptor-dependent ABC-type nutrient uptake porters. Res. Microbiol. 146: 271-278.

Lambert, A., M. Østeras, K. Mandon, M.-C. Poggi, and D. Le Rudulier. (2001). Fructose uptake in Sinorhizobium meliloti is mediated by a high-affinity ATP-binding cassette transport system. J. Bacteriol. 183: 4709-4717.

Linton, K.J. and C.F Higgins. (1998). The Escherichia coli ATP-binding cassette (ABC) proteins. Mol. Microbiol. 28: 5-13.

Locher, K.P., A.T. Lee, and D.C. Rees. (2002). The E. coli BtuCD structure: A framework for ABC transporter architecure and mechanism. Science 296: 1091-1098.

Maeda, S. and T. Omata. (1997). Substrate-binding lipoprotein of the cyanobacterium Synechococcus sp. strain PCC7942 involved in the transport of nitrate and nitrite. J. Biol. Chem. 272: 3036-3041.

Makdessi, K., J.R. Andreesen, and A. Pich. (2001). Tungstate uptake by a highly specific ABC transporter in Eubacterium acidaminophilum. J. Biol. Chem. 276: 24557-24564.

Mishima, Y., K. Momma, W. Hashimoto, B. Mikami, and K. Murata. (2001). Super-channel in bacteria: function and structure of the macromolecule import system mediated by a pit-dependent ABC transporter. FEMS Microbiol. Lett. 204: 215-221.

Momma, K., M. Okamoto, Y. Mishima, S. Mori, W. Hashimoto, and K. Murata. (2000). A novel bacterial ATP-binding cassette transporter system that allows uptake of macromolecules. J. Bacteriol. 182: 3998-4004.

Narita, S., K. Tanaka, S. Matsuyama, and H. Tokuda. (2002). Disruption of lolCDE, encoding an ATP-binding cassette transporter, is lethal for Escherichia coli and prevents release of lipoproteins from the inner membrane. J. Bacteriol. 184: 1417-1422.

Obis, D., A. Guillot, J.-C. Gripon, P. Renault, A. Bolotin, and M.-Y. Mistou. (1999). Genetic biochemical characterization of a high-affinity betaine uptake system (BusA) in Lactococcus lactis reveals a new functional organization within bacterial ABC transporters. J. Bacteriol. 181: 6238-6246.

Park, J.T., D. Raychaudhuri, H. Li, S. Normark, and D. Mengin-Lecreulx. (1998). MppA, a periplasmic binding protein essential for import of the bacterial cell wall peptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate. J. Bacteriol. 180: 1215-1223.

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Saurin, W., M. Hofnung, and E. Dassa. (1998). Getting in or out. Early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. J. Mol. Evol. 48: 22-41.

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Tam, R. and M.H. Saier, Jr. (1993). Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Microbiol. Rev. 57: 320-346.

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Walshaw, D.L. and P.S. Poole. (1996). The general L-amino acid permease of Rhizobium leguminosarum is an ABC uptake system that also influences efflux of solutes. Mol. Microbiol. 21: 1239-1252.

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ABC-type Efflux Porters (Bacterial)

Akatsuka, H., E. Kawai, K. Omori, and T. Shibatani. (1995). The three genes lipB, lipC,and lipD involved in the extracellular secretion of the Serratia marcescens lipase which lacks and N-terminal signal peptide. J. Bacteriol. 177: 6381-6389.

Awram, P. and J. Smit. (1998). The Caulobacter crescentus paracrystalline S-layer protein is secreted by an ABC transporter (Type I) secrection apparatus. J. Bacteriol. 180: 3062-3069.

Binet, R., S. Létoffé, J.M. Ghigo, P. Delepelaire, and C. Wanderman. (1997). Protein secretion by Gram-negative bacterial ABC exporters – a review. Gene 192: 7-11.

Chang, G. (2003). Structure of MsbA from Vibrio cholera: a multidrug resistance ABC transporter homolog in a closed conformation. J. Mol. Biol. 330: 419-430.

Chang, G. and C.B. Roth. (2001). Structure of MsbA from E. coli: A homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293: 1793-1800.

Chater, K.F. and S. Horinouchi. (2003). Signalling early developmental events in two highly diverged Streptomyces species. Mol. Microbiol. 48: 9-15.

Cheng, J., A.A. Guffanti, and T.A. Krulwich. (1997). A two-gene ABC-type transport system that extrudes Na⁺ in Bacillus subtilis is induced by ethanol or protonophore. Mol. Microbiol. 23: 1107-1120.

Doerrler, W.T., M.C. Reedy, and C.R.H. Raetz. (2001). An Escherichia coli mutant defective in lipid export. J. Biol. Chem. 276: 11461-11464.

Espinasse, S., M. Gohar, D. Lereclus, and V. Sanchis. (2002). An ABC transporter from Bacillus thuringiensis is essential for β-exotoxin I production. J. Bacteriol. 184: 5848-5854.

Fath, M.J. and R. Kolter. (1993). ABC transporters: bacterial exporters. Microbiol. Rev. 57: 995-1017.

Feng, L., S.N. Senchenkova, J. Yang, A.S. Shashkov, J. Tao, H. Guo, J. Cheng, Y. Ren, Y.A. Knirel, P.R. Reeves, and L. Wang. (2004). Synthesis of the heteropolysaccharide O antigen of Escherichia coli O52 requires an ABC transporter: structural and genetic evidence. J. Bacteriol. 186: 4510-4519.

Fiedler, G., M. Arnold, S. Hannus, and I. Maldener. (1998). The DevBCA exporter is essential for envelope formation in heterocysts of the cyanobacterium Anabaena sp. strain PCC7120. Mol. Microbiol. 27: 1193-1202.

Garault, P., D. Le Bars, C. Besset, and V. Monnet. (2002). Three oligopeptide-binding proteins are involved in the oligopeptide transport of Streptococcus thermophilus. J. Biol. Chem. 277: 32-39.

González-Pastor, J.E., E.C. Hobbs, and R. Losick. (2003). Cannibalism by sporulating bacteria. Science 301: 510-513.

Haney, D.Q. (1999). New class of antibiotics may help doctors overcome resistant germs. Assoc. Press.

Hinsa, S.M., M. Espinosa-Urgel, J.L. Ramos, and G.A. O'Toole. (2003). Transition from reversible to irreversible attachment during biofilm formation by Pseudomonas fluorescens WCS365 requires an ABC transporter and a large secreted protein. Mol. Microbiol. 49: 905-918.

Igarashi, Y., K.F. Aoki, H. Mamitsuka, K. Kuma, and M. Kanehisa. (2004). The evolutionary repertoires of the eukaryotic-type ABC transporters in terms of the phylogeny of ATP-binding domains in eukaryotes and prokaryotes. Mol. Biol. Evol. (in press).

Kawai, E., H. Akatsuka, A. Idei, T. Shibatani, and K. Omori. (1998). Serratia marcescens S-layer protein is secreted extracellularly via an ATP-binding cassette exporter, the Lip system. Mol. Microbiol. 27: 941-952.

Kobayashi, N., K. Nishino, and A. Yamaguchi. (2001). Novel macrolide-specific ABC-type efflux transporter in Escherichia coli. J. Bacteriol. 183: 5639-5644.

McAuliffe, O., R.P. Ross, and C. Hill. (2001). Lantibiotics: structure, biosynthesis and mode of action. FEMS Microbiol. Rev. 25: 285-308.

Méndez, C. and J.A. Salas. (1998). ABC transporters in antibiotic-producing actinomycetes. FEMS Microbiol. Lett. 158: 1-8.

Narita, S., K. Kanamaru, S. Matsuyama, and H. Tokuda. (2003). A mutation in the membrane subunit of an ABC transporter LolCDE complex causing outer membrane localization of lipoproteins against their inner membrane-specific signals. Mol. Microbiol. 49: 167-177.

Netz, D.J.A., H.-G. Sahl, R. Marcolino, J.S. Nascimento, S.S. Oliveira, M.B. Soares, and M.C.F. Bastos. (2001). Molecular characterisation of Aureocin A70, a multipeptide bacteriocin isolated from Staphylococcus aureus. J. Mol. Biol. 311: 939-949.

Ohki, R., Giyanto, K. Tateno, W. Masuyama, S. Moriya, K. Kobayashi, and N. Ogasawara. (2003). The BceRS two-component regulatory system induces expression of the bacitracin transporter, BceAB, in Bacillus subtilis. Mol. Microbiol. 49: 1135-1144.

Paulsen, I.T., A.M. Beness, and M.H. Saier, Jr. (1997). Computer-based analyses of the protein constituents of transport systems catalyzing export of complex carbohydrates in bacteria. Microbiology 143: 2685-2699.

Reuter, G., T. Janvilisri, H. Venter, S. Shahi, L. Balakrishnan, and H.W. van Veen. (2003). The ATP binding cassette multidrug transporter LmrA and lipid transporter MsbA have overlapping substrate specificities. J. Biol. Chem. 278: 35193-35198.

Schmitt, L. and R. Tampé. (2002). Structure and mechanism of ABC transporters. Curr. Opin. Struct. Biol. 12: 754-760.

Schulz, H., R.A. Fabianek, E.C. Pellicioli, H. Hennecke, and L. Thöny-Meyer. (1999). Heme transfer to the heme chaperone CcmE during cytochrome c maturation requires the CcmC protein, which may function independently of the ABC-transporter CcmAB. Proc. Natl. Acad. Sci. USA 96: 6462-6467.

Solbiati, J.O., M. Ciaccio, R.N. Farias, J.E. Gonzalez-Pastor, F. Moreno, and R.A. Salomon. (1999). Sequence analysis of the four plasmid genes required to produce the circular peptide antibiotic microcin J25. J. Bacteriol. 181: 2659-2662.

Tauch, A., S. Krieft, A. Pühler, and J. Kalinowski. (1999). The tetAB genes of the Corynebacterium striatum R-plasmid pTP10 encode an ABC transporter and confer tetracycline, oxytetracycline and oxacillin resistance in Corynebacterium glutamicum. FEMS Microbiol. Lett. 173: 203-209.

Thompson, S.A., O.L. Shedd, K.C. Ray, M.H. Beins, J.P. Jorgensen, and M.J. Blaser. (1998). Campylobacter fetus surface layer proteins are transported by a type I secretion system. J. Bacteriol. 180: 6450-6458.

Thöny-Meyer, L. (1997). Biogenesis of respiratory cytochromes in bacteria. Microbiol. Mol. Biol. Rev. 61: 337-376.

Tjalsma, H., A. Bolhuis, J.D.H. Jongbloed, S. Bron, and J.M. van Dijl. (2000). Signal peptide-dependent protein transport in Bacillus subtilis: a genome-based survey of the secretome. Microbiol. Mol. Biol. Rev. 64: 515-547.

Ueda, K., K.-I. Oinuma, G. Ideka, K. Hosono, Y. Ohnishi, S. Horinouchi, and T. Beppu. (2002). AmfS, an extracellular peptidic morphogen in Streptomyces griseus. J. Bacteriol. 184: 1488-1492.

van Veen, H.W. and W.N. Konings. (1998). The ABC family of multidrug transporters in microorganisms. Biochim. Biophys. Acta 1365: 31-36.

van Veen, H.W., A. Margolles, M. Müller, C.F. Higgins, and W.N. Konings. (2000). The homodimeric ATP-binding cassette transporter LmrA mediates multidrug transport by an alternating two-site (two-cylinder engine) mechanism. EMBO J. 19: 2503-2514.

Walshaw, D.L. and P.S. Poole. (1996). The general L-amino acid permease of Rhizobium leguminosarum is an ABC uptake system that also influences efflux of solutes. Mol. Microbiol. 21: 1239-1252.

Young, J. and I.B. Holland. (1999). ABC transporters: bacterial exporters-revisited five years on. Biochim. Biophys. Acta 1461: 177-200.

ABC-type Efflux Porters (Mostly Eukaryotic)

Abele, R. and R. Tampè. (1999). Function of the transport complex TAP in cellular immune recognition. Biochim. Biophys. Acta 1461: 405-419.

Akabas, M.H. (2000). Cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 275: 3729-3732.

Andrade, A.C., G. Del Sorbo, J.G.M. Van Nistelrooy, and M.A. De Waard. (2000). The ABC transporter AtrB from Aspergillus nidulans mediates resistance to all major classes of fungicides and some natural toxic compounds. Microbiology 146: 1987-1997.

Anjard, C., the Dictyostelium Sequencing Consortium, and W.F. Loomis. (2002). Evolutionary analyses of ABC transporters of Dictyostelium discoideum. Eukaryotic Cell 1: 643-652.

Balzi, E., M. Wang, S. Leterme, L. Van Dyck, and A. Goffeau. (1994). PDR5, a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1. J. Biol. Chem. 269: 2206-2214.

Bauer, B.E., H. Wolfger, and K. Kuchler. (1999). Inventory and function of yeast ABC protein: about sex, stress, pleiotropic drug and heavy metal resistance. Biochim. Biophys. Acta 1461: 217-236.

Bellamy, W.T. (1996). P-glycoproteins and multidrug resistance. Ann. Rev. Pharmcol. Toxicol. 36: 161-183.

Borst, P., R. Evers, M. Kool, and J. Wijnholds. (1999). The multidrug resistance protein family. Biochim. Biophys. Acta 1461: 347-357.

Borst, P. and R.O. Elferink. (2002). Mammalian ABC transporters in health and disease. Annu. Rev. Biochem. 71: 537-592.

Bryan, J. and L. Aguilar-Bryan. (1999). Sulfonylurea receptors: ABC transporters that regulate ATP-sensitive K⁺ channels. Biochim. Biophys. Acta 1461: 285-303.

Clement, J.P., IV, K. Kunjilwar, G. Gonzalez, M. Schwanstecher, U. Panten, L. Aguilar-Bryan, and J. Bryan. (1997). Association and stoichiometry of K_ATP channel subunits. Neuron 18: 827-838.

Dean, M. and R. Allikmets. (2001). Complete characterization of the human ABC gene family. J. Bioenerg. Biomembr. 33: 475-479.

Decottignies, A. and A. Goffeau. (1997). Complete inventory of the yeast ABC proteins. Nat. Genet. 15: 137-145.

Falcòn-Pèrez, J.M., M.J. Mazòn, J. Molano, and P. Eraso. (1999). Functional domain analysis of the yeast ABC transporter Ycf1p by site-directed mutagenesis. J. Biol. Chem. 274: 23584-23590.

Francis, G.A., M. Tsujita, and T.L. Terry. (1999). Apolipoprotein A1 efficiently binds to and mediates cholesterol and phospholipid efflux from human but not rat aortic smooth muscle cells. Biochemistry 38: 16315-16322.

Garrigues, A., A.E. Escargueil, and S. Orlowski. (2002). The multidrug transporter, P-glycoprotein, actively mediates cholesterol redistribution in the cell membrane. Proc. Natl. Acad. Sci. USA 99: 10347-10352.

Gottesman, M.M., C.A. Hrycyna, P.V. Schoenlein, U.A. Germann, and I. Pastan. (1995). Genetic analysis of the multidrug transporter. Annu. Rev. Genet. 29: 607-649.

Green, R.M., F. Hoda, and K.L. Ward. (2000). Molecular cloning and characterization of the murine bile salt export pump. Gene 241: 117-123.

Guo, Y., E. Kotova, Z.-S. Chen, K. Lee, E. Hopper-Borge, M.G. Belinsky, and G.D. Kruh. (2003). MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine. J. Biol. Chem. 278: 29509-29514.

Haimeur, A., R.G. Deeley, and S.P.C. Cole. (2002). Charged amino acids in the sixth transmembrane helix of multidrug resistance protein 1 (MRP1/ABCC1) are critical determinants of transport activity. J. Biol. Chem. 277: 41326-41333.

Hettema, E.H., C.W.T. van Roermund, B. Distel, M. van den Berg, C. Vilela, C. Rodrigues-Pousada, R.J.A. Wanders, and H.F. Tabak. (1996). The ABC transporter proteins Pat1 and Pat2 are required for import of long-chain fatty acids into peroxisomes of Saccharomyces cerevisiae. EMBO J. 15: 3813-3822.

Higgins, C.F. (1995). The ABC of channel regulation. Cell 82: 693-696.

Holland, B. and M.A. Blight. (1999). ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans. J. Mol. Biol. 293: 381-399.

Hou, Y., J.R. Riordan, and X. Chang. (2003). ATP binding, not hydrolysis, at the first nucleotide-binding domain of multidrug resistance-associated protein MRP1 enhances ADP^.Vi trapping at the second domain. J. Biol. Chem. 278: 3599-3605.

Iliás, A., Z. Urbán, T.L. Seidl, O. Le Saux, E. Sinkó, C.D. Boyd, B. Sarkadi, and A. Várdi. (2002). Loss of ATP-dependent transport activity in Pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J. Biol. Chem. 277: 16860-16867.

Janas, E., M. Hofacker, M. Chen, S. Gompf, C. van der Does, and R. Tampé. (2003). The ATP hydrolysis cycle of the nucleotide-binding domain of the mitochondrial ATP-binding cassette transporter Mdl1p. J. Biol. Chem. 278: 26862-26869.

Janvilisri, T., H. Venter, S. Shahi, G. Reuter, L. Balakrishnan, and H.W. van Veen. (2003). Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J. Biol. Chem. 278: 20645-20651.

Jedlitschky, G., B. Burchell, and D. Keppler. (2000). The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J. Biol. Chem. 275: 30069-30074.

Kala, S.V., M.W. Neely, G. Kala, C.I. Prater, D.W. Atwood, J.S. Rice, and M.W. Lieberman. (2000). The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. J. Biol. Chem. 275: 33404-33408.

Keppler, D. (1999). Export pumps for glutathione S-conjugates. Free Rad. Biol. Med. 27: 985-991.

Keppler, D. and J. König. (1997). Expression and localization of the conjugate export pump encoded by the MRP2(cMRP/cMOAT) gene in liver. FASEB J. 11: 509-516.

Klein, I., B. Sarkadi, and A. Vàradi. (1999). An inventory of the human ABC proteins. Biochim. Biophys. Acta 1461: 237-262.

Kogan, I., M. Ramjeesingh, C. Li, J.F. Kidd, Y. Wang, E.M. Leslie, S.P.C. Cole, and C.E. Bear. (2003). CFTR directly mediates nucleotide-regulated glutathione flux. EMBO J. 22: 1981-1989.

Lange, H., G. Kispal, and R. Lill. (1999). Mechanism of iron transport to the site of heme synthesis inside yeast mitochondria. J. Biol. Chem. 274: 18989-18996.

Légaré, D., D. Richard, R. Mukhopadhyay, Y.-D. Stierhof, B.P. Rosen, A. Haimeur, B. Papadopoulou, and M. Ouellette. (2001). The Leishmania ATP-binding cassette protein PGPA is an intracellular metal-thiol transporter ATPase. J. Biol. Chem. 276: 26301-26307.

Leslie, E.M., A. Haimeur, and M.P. Waalkes. (2004). Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required. J. Biol. Chem. 279: 32700-32708.

Liu, G., R. Sánchez-Fernández, Z-S. Li, and P.A. Rea. (2001). Enhanced multispecificity of Arabidopsis vacuolar multidrug resistance-associated protein-type ATP-binding cassette transporter, AtMRP2. J. Biol. Chem. 276: 8648-8656.

Loo, T.W., M.C. Bartlett, and D.M. Clarke. (2003). Drug binding in human P-glycoprotein causes conformational changes in both nucleotide-binding domains. J. Biol. Chem. 278: 1575-1578.

Mahé, Y., Y. Lemoine, and K. Kuchler. (1996). The ATP binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. J. Biol. Chem. 271: 25167-25172.

Mao, Q., R.G. Deeley, and S.P.C. Cole. (2000). Functional reconstitution of substrate transport by purified multidrug resistance protein MRP1 (ABCC1) in phospholipid vesicles. J. Biol. Chem. 275: 34166-34172.

Mitsubashi, N., T. Miki, H. Senbongi, N. Yokoi, H. Yano, M. Miyazaki, N. Nakajima, T. Iwanaga, Y. Yokoyama, T. Shibata, and S. Seino. (2000). MTABC3, a novel mitochondrial ATP-binding cassette protein involved in iron homeostasis. J. Biol. Chem. 275: 17536-17540.

Mühlenhoff, U. and R. Lill. (2000). Biogenesis of iron-sulfur proteins in eukaryotes: a novel task of mitochondria that is inherited from bacteria. Biochim. Biophys. Acta 1459: 370-382.

Neumann, L. and R. Tampé. (1999). Kinetic analysis of peptide binding to the TAP transport complex: evidence for structural rearrangements induced by substrate binding. J. Mol. Biol. 294: 1203-1213.

Ortiz, D.F., L. Kreppel, D.M. Speiser, G. Scheel, G. McDonald, and D.W. Ow. (1992). Heavy metal tolerance in the fission yeast requires an ATP-binding cassette-type vacuolar membrane transporter. EMBO J. 11: 3491-3499.

Posteraro, B., M. Sanguinetti, D. Sanglard, M. La Sorda, S. Boccia, L. Romano, G. Morace, and G. Fadda. (2003). Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol. Microbiol. 47: 357-371.

Raghuraman, G. P.E. Lapinski, and M. Raghavan. (2002). Tapasin interacts with the membrane-spanning domains of both TAP subunits and enhances the structural stability of TAP1^.TAP2 complexes. J. Biol. Chem. 277: 41786-41794.

Reid, G., P. Wielinga, N. Zelcer, I. van der Heijden, A. Kuil, M. de Haas, J. Wijnholds, and P. Borst. (2003). The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc. Natl. Acad. Sci. USA 100: 9244-9249.

Rosenberg, M.F., A.B. Kamis, R. Callaghan, C.F. Higgins, and R.C. Ford. (2003). Three-dimensional structures of the mammalian multidrug resistance P-glycoprotein demonstrate major conformational changes in the transmembrane domains upon nucleotide binding. J. Biol. Chem. 278: 8294-8299.

Ruknudin, A., D.H. Schulze, S.K. Sullivan, W.J. Lederer, and P.A. Welling. (1998). Novel subunit composition of a renal epithelial K_ATP channel. J. Biol. Chem. 273: 14165-14171.

Schuetzer-Muehlbauer, M., B. Willinger, G. Krapf, S. Enzinger, E. Presterl, and K. Kuchler. (2003). The Candida albicans Cdr2p ATP-binding cassette (ABC) transporter confers resistance to caspofungin. Mol. Microbiol. 48: 225-235.

Shani, N., P.A. Watkins, and D. Valle. (1995). PXA1, a possible Saccharomyces cerevisiae ortholog of the human adrenoleukodystrophy gene. Proc. Natl. Acad. Sci. USA 92: 6012-6016.

Smith, A.J., A. van Helvoort, G. van Meer, K. Szabó, E. Welker, G. Szakács, A. Váradi, B. Sarkadi, and P. Borst. (2000). MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J. Biol. Chem. 275: 23530-23539.

van Endert, P.M. (1999). Role of nucleotides and peptide substrate for stability and functional state of the human ABC family transporters associated with antigen processing. J. Biol. Chem. 274: 14632-14638.

Young, L., K. Leonhard, T. Tatsuta, J. Trowsdale, and T. Langer. (2001). Role of the ABC transporter Mdl1 in peptide export from mitochondria. Science 291: 2135-2137.

Xu, J., Y. Liu, Y. Yang, S. Bates, and J.-T. Zhang. (2004). Characterization of oligomeric human half-ABC transporter ATP-binding cassette G2. J. Biol. Chem. 279: 19781-19789.

Macromolecular structures of proteins in this family:

3.A.1.1.1 - 1ANF
3.A.1.1.1 - 4MBP
3.A.1.1.1 - 3MBP
3.A.1.106.1 - 1JSQ
3.A.1.106.1 - 1PF4
3.A.1.13.1 - 1L7V
3.A.1.13.1 - 1N2Z

References:

The references are listed above in the description.

Examples:

TC#

Name

Organismal Type

Example

3.A.1.1 The Carbohydrate Uptake Transporter-1 (CUT1) Family

3.A.1.1.1

Maltooligosaccharide porter

MalEFGK of E. coli
MalE (receptor [R])
MalF (membrane [M])
MalG (membrane [M])
MalK (cytoplasmic [C])

3.A.1.1.2

Multiple sugar (melibiose; raffinose, etc.) porter

MsmEFGK of Streptococcus mutans
MsmE (R)
MsmF (M)
MsmG (M)
MsmK (C)

3.A.1.1.3

Glycerol-phosphate porter

UgpABCE of E. coli
UgpB (R)
UgpA (M)
UgpE (M)
UgpC (C)

3.A.1.1.4

Lactose porter

LacEFGK of Agrobacterium radiobacter
LacE (R)
LacF (M)
LacG (M)
LacK (C)

3.A.1.1.5

Hexitol (glucitol; mannitol) porter

SmoEFGK of Rhodobacter sphaeroides
SmoE (R)
SmoF (M)
SmoG (M)
SmoK (C)

3.A.1.1.6

Cyclodextrin porter

CymDEFG of Klebsiella oxytoca
CymE (R)
CymF (M)
CymG (M)
CymD (C)

3.A.1.1.7

Maltose/trehalose porter

MalEFGK of Thermococcus litoralis
MalE (R)
MalF (M)
MalG (M)
MalK (C) (not sequenced)

3.A.1.1.8

Sucrose/maltose/trehalose porter (sucrose-inducible)

AglEFGK of Sinorhizobium meliloti
AglE (R)
AglF (M)
AglG (M)
AglK (C)

3.A.1.1.9

α-D-glucuronate porter

GuaEFG(K?) of Bacillus stearothermophilus
GuaE (Orf2) (R)
GuaF (Orf3) (M)
GuaG (Orf4) (M)
GuaK (C) (not sequenced)

3.A.1.1.10

Alginate (MW 27,000 Da) (and Alginate oligosaccharides) uptake porter

AlgSM1M2Q1Q2 of Sphingomonas sp.A1
AlgS (C)
AlgM1 (M)
AlgM2 (M)
AlgQ1 (R)
AlgQ2 (R)

3.A.1.1.11

Saturated and unsaturated oligogalacturonide transporter, TogMNAB (transports di- to tetrasaccharide pectin degradation products which consist of D-galacuronate, sometimes with 4-deoxy-L-threo-5-hexosulose uronate at the reducing end of the oligosaccharide)

Oligogalacturonide transporter TogMNAB of Erwinia chrysanthemi
TogM (M)
TogN (M)
TogA (C)
TogB (R)

3.A.1.1.12

Palatinose (isomaltulose; 6-O-α-D-glucopyranosyl-D-fructose) uptake porter

PalEFGK of Erwinia rhapontici
PalE (R)
PalF (M)
PalG (M)
PalK (C)

3.A.1.1.13

Glucose, mannose, galactose porter

GlcSTUV of Sulfolobus solfataricus
GlcS (R)
GlcT (M)
GlcU (M)
GlcV (C)

3.A.1.1.14

Arabinose, fructose, xylose porter

AraSTUV of Sulfolobus solfataricus
AraS (R)
AraT (M)
AraU (M)
AraV (C)

3.A.1.1.15

Trehalose porter

TreSTUV of Sulfolobus solfataricus
TreS (R)
TreT (M)
TreU (M)
TreV (C)

3.A.1.1.16

Maltooligosaccharide porter (Maltose is not a substrate, but maltotriose is.)

PF1933, 1936, 1937, 1938 of Pyrococcus furiosus
PF1938 (R)
PF1937 (M)
PF1936 (M)
PF1933 (C)

3.A.1.1.17

Trehalose/maltose/sucrose porter (trehalose inducible)

ThuEFGK of Sinorhizobium meliloti
ThuE (R)
ThuF (M)
ThuG (M)
ThuK (C)

3.A.1.1.18

N-Acetylglucosamine/N,N'-diacetyl chitobiose porter

NgcEFG of Streptomyces olivaceoviridis
NgcE (R)
NgcF (M)
NgcG (C)

3.A.1.1.19

Platinose (isomaltulose) (6-O-α-D-glucopyranosyl-D-fructofuranose) porter

PalEFGK of Agrobacterium tumefaciens
PalE (R)
PalF (M)
PalG (M)
PalK (C)

3.A.1.1.20

The fructooligosaccharide porter, MsmEFGK (Barrangou et al., 2003)

Bacteria

MsmEFGK of Lactobacillus acidophilus
MsmE (R) AAO21856
MsmF (M) AAO21857
MsmG (M) AAO21858
MsmK (C) AAO21860

3.A.1.1.21

The xylobiose porter; BxlEFG(K) (Tsujibo et al., 2004)

Bacteria

BxlEFGK of Streptomyces thermoviolaceus
BxlE (R) CAB88161
BxlF (M) CAB88162
BxlG (M) CAB88163
BxlK (C) Unknown

3.A.1.2 The Carbohydrate Uptake Transporter-2 (CUT2) Family

3.A.1.2.1

Ribose porter (RbsC has 10 TMSs with N- and C-termini in the cytoplasm (Stewart and Heimodson, 2003))

RbsABCD of E. coli
RbsB (R)
RbsC (M)
RbsD (M)
RbsA (C)

3.A.1.2.2

Arabinose porter

AraFGH of E. coli
AraF (R)
AraG (C)
AraH (M)

3.A.1.2.3

Galactose/glucose (methyl galactoside) porter

MglABC of E. coli
MglA (C)
MglB (R)
MglC (M)

3.A.1.2.4

Xylose porter

XylFGH of E. coli
XylF (R)
XylG (C)
XylH (M)

3.A.1.2.5

Multiple sugar (arabinose, xylose, galactose, glucose, fucose) putative porter

ChvE, GguAB of Agrobacterium tumefaciens
ChvE (R)
GguA (C)
GguB (M)

3.A.1.2.6

D-allose porter

AlsABC of E. coli
AlsB (R)
AlsA (C)
AlsC (M)

3.A.1.2.7

Fructose/mannose/ribose porter

FrcABC of Sinorhizobium meliloti
FrcA (C)
FrcB (R)
FrcC (M)

3.A.1.2.8

AI2 autoinducer porter (Taga et al., 2001, 2004)

LsrACDB of E. coli
LsrB (R) AAC74589
LsrA (C) AAC74586
LsrC (M) AAC74587
LsrD (M) AAC74588

3.A.1.2.9

Rhamnose porter (Richardson et al., 2004)

RhaSTP of Rhizobium leguminosarum bv. trifolii
RhaS (R) AAQ92407
RhaT (C) AAQ92408
RhaP (M) AAQ92409

3.A.1.3 The Polar Amino Acid Uptake Transporter (PAAT) Family

3.A.1.3.1

Histidine; arginine/lysine/ornithine porter

HisJ (histidine receptor)-ArgT (arg/lys/orn receptor)-HisMPQ of Salmonella typhimurium
HisJ (R)
ArgT (R)
HisM (M)
HisQ (M)
HisP (C)

3.A.1.3.2

Glutamine porter

GlnHPQ of E. coli
GlnH (R)
GlnP (M)
GlnQ (C)

3.A.1.3.3

Arginine porter

ArtI (arginine receptor #1)/ArtJ (arginine receptor #2)-ArtMQP of E. coli
ArtP (C)
ArtQ (M)
ArtM (M)
ArtJ (R)
ArtI (R)

3.A.1.3.4

Glutamate/aspartate porter

GltIJKL of E. coli
GltI (R)
GltJ (M)
GltK (M)
GltL (C)

3.A.1.3.5

Octopine porter

OccQMPT of Agrobacterium tumefaciens
OccT (R)
OccQ (M)
OccM (M)
OccP (C)

3.A.1.3.6

Nopaline porter

NocQMPT of Agrobacterium tumefaciens
NocT (R)
NocQ (M)
NocM (M)
NocP (C)

3.A.1.3.7

Glutamate/glutamine/aspartate/asparagine porter

BztABCD of Rhodobacter capsulatus
BztA (R)
BztB (M)
BztC (M)
BztD (CC)

3.A.1.3.8

General L-amino acid porter; transports basic and acidic amino acids preferentially, but also transports aliphatic amino acids (catalyzes both uptake and efflux)

AapJQMP of Rhizobium leguminosarum
AapJ (R)
AapQ (M)
AapM (M)
AapP (C)

3.A.1.3.9

Glutamate porter

GluABCD of Corynebacterium glutamicum
GluA (C)
GluB (R)
GluC (M)
GluD (M)

3.A.1.3.10

Cystine/diaminopimelate

Cys/Dap porter of E. coli
CysX (R)
CysY (M)
CysZ (C)

3.A.1.3.11

Arginine/ornithine (but not lysine) porter

AotJQMP of Pseudomonas aeruginosa
AotJ (R)
AotQ (M)
AotM (M)
AotP (C)

3.A.1.3.12

Arginine/lysine/histidine/glutamine porter

BgtAB of Synechocystis PCC6803
BgtA (C)
BgtB (R-M)

3.A.1.3.13

Uptake system for L-cystine (Km=2.5 μM), L-cystathionine, L-djenkolate, and S-methyl-L-cysteine (Burguière et al., 2004)

TcyJKLMN (YtmJKLMN) of Bacillus subtilis
TcyJ (R) (NP_390816)
TcyK (R) (O34852)
TcyL (M) (O34315)
TcyM (M) (O34931)
TcyN (C) (O34900)

3.A.1.3.14

Uptake system for L-cystine (Burguière et al., 2004)

TcyABC (YckKJI) of Bacillus subtilis
TcyA (R) (P42199)
TcyB (M) (P42200)
TcyC (C) (P39456)

3.A.1.4 The Hydrophobic Amino Acid Uptake Transporter (HAAT) Family

3.A.1.4.1

Leucine; leucine/isoleucine/valine porter (also transports phenylalanine and tyrosine; Koyanagi et al., 2004)

LivK (leucine-specific receptor)-LivJ (Leu/Ile/Val receptor)-LivHMGF of E. coli
LivJ (R)
LivK (R)
LivH (M)
LivM (M)
LivG (C)
LivF (C)

3.A.1.4.2

Leucine/proline/alanine/serine/glycine (and possibly histidine) porter

NatA-E neutral amino acid porter of Synechocystis sp.PCC6803
NatA (C)
NatB (R)
NatC (M)
NatD (M)
NatE (C)

3.A.1.4.3

General L- (and D-)amino acid uptake porter (transports acidic, basic, polar, semipolar and hydrophobic amino acids). The amino and carboxyl groups do not need to be α since γ-aminobutyric acid (GABA) is a substrate. The system may function with additional binding proteins since L-alanine uptake is not dependent on BraC.

BraCDEF of Rhizobium leguminosarum
BraC (R)
BraD (M)
BraE (M)
BraF (C)

3.A.1.4.4

The high-affinity (<1 μM) urea porter

UrtA-E urea porter of Anabaena sp. PCC7120
UrtA (R)
UrtB (M)
UrtC (M)
UrtD (C)
UrtE (C)

3.A.1.4.5

The high affinity urea/thiourea/hydroxyurea porter (Beckers et al., 2004)

UrtA-E of Corynebacterium glutamicum
UrtA (R) CAF19637
UrtB (M) CAF19636
UrtC (M) CAF19638
UrtD (C) CAF19639
UrtE (C) CAF19640

3.A.1.5 The Peptide/Opine/Nickel Uptake Transporter (PepT) Family

3.A.1.5.1

Oligopeptide porter (also takes up amino glycoside antibiotics such as kanamycin, streptomycin and neomycin as well as cell wall-derived peptides such as murein tripeptide). It transports substrate peptides of 2-5 amino acids with highest affinity for tripeptides. Also transports δ-aminolevulinic acid (ALA). [May be regulated by PTS Enzyme I^Ntr-aspartokinase.]

OppABCDF of Salmonella typhimurium
OppA (R)
OppB (M)
OppC (M)
OppD (C)
OppF (C)
MppA (R) (in E. coli)

3.A.1.5.2

Dipeptide porter. Also transports δ-aminolevulinic acid (ALA)

DppABCDE of Bacillus subtilis
DppA (C)
DppB (M)
DppC (M)
DppD (C)
DppE (R)

3.A.1.5.3

Nickel porter

NikABCDE of E. coli
NikA (R)
NikB (M)
NikC (M)
NikD (C)
NikE (C)

3.A.1.5.4

Agrocinopine (an opine)/Agrocin 84 (an antibiotic) porter

AccABCDE of Agrobacterium tumefaciens
AccA (R)
AccB (C)
AccC (C)
AccD (M)
AccE (M)

3.A.1.5.5

Probable cationic peptide porter (may also take up peptide antibiotics and protamine; implicated in K⁺ homeostasis) [SapD can stimulate the K⁺ uptake activities of TrkH and TrkG (TC #2.A.38.1.1) in the presence of ATP.]

SapABCDF of Salmonella typhimurium
SapA (R)
SapB (M)
SapC (M)
SapD (C)
SapF (C)

3.A.1.5.6

The β-glucoside (cellobiose (β-1,4), cellotriose, cellotetraose, cellopentaose, laminaribiose (β-1,3), laminaritriose, sophorose) uptake porter, CbtABCDF

Archaea

The β-glucoside uptake porter of Pyrococcus furiosus, CbtABCDF
CbtA (R)
CbtB (M)
CbtC (M)
CbtD (C)
CbtF (C)

3.A.1.5.7

The α-galactoside (melibiose, raffinose) uptake porter, AgpABCDF

Bacteria

The α-galactoside uptake porter of Rhizobium meliloti
AgpA (R)
AgpB (M) (not identified)
AgpC (M) (not identified)
AgpD (C) (not identified)
AgpF (C) (not identified)

3.A.1.5.8

Maltose and maltooligosaccharide porter

MalEFGK of Sulfolobus solfataricus
MalE (R)
MalF (M)
MalG (M)
MalK (C)

3.A.1.5.9

Cellobiose and cellooligosaccharide porter

CbtABCDF of Sulfolobus solfataricus
CbtA (R)
CbtB (M)
CbtC (M)
CbtD (C)
CbtF (C)

3.A.1.5.10

Oligopeptide porter (transports peptides of 4-35) amino acyl residues; di- and tripeptides are not transported; hydrophobic basic peptides are preferred). OppA determines the specificity of the system (Doeven et al., 2004).

OppABCDF of Lactococcus lactis
OppA (R) (NP_267994)
OppB (M) (NP_267996)
OppC (M) (NP_267995)
OppD (C) (NP_267998)
OppF (C) (NP_267997)

3.A.1.6 The Sulfate/Tungstate Uptake Transporter (SulT) Family

3.A.1.6.1

Sulfate/thiosulfate porter

Sbp (sulfate receptor)-CysP (thiosulfate receptor)-CysTWA of E. coli
Sbp (R)
CysP (R)
CysT (M)
CysW (M)
CysA (C)

3.A.1.6.2

Tungstate porter

TupABC of Eubacterium acidaminophilum
TupA (R)
TupB (M)
TupC (C)

3.A.1.6.3

Sulfate porter

CysAWT SubI-sulfate porter of Mycobacterium tuberculosis
CysA (C)
CysW (M)
CysT (M)
SubI (R)

3.A.1.7 The Phosphate Uptake Transporter (PhoT) Family

3.A.1.7.1

Phosphate porter

PhoS (phosphate receptor)-PstABC of E. coli
PhoS (R)
PstA (M)
PstC (C)
PstB (C)

3.A.1.8 The Molybdate Uptake Transporter (MolT) Family

3.A.1.8.1

Molybdate porter

ModABC of E. coli
ModA (R)
ModB (M)
ModC (C)

3.A.1.9 The Phosphonate Uptake Transporter (PhnT) Family

3.A.1.9.1

Phosphonate/organophosphate ester porter (broad specificity)

PhnCDE of E. coli
PhnC (C)
PhnD (R)
PhnE (M)

3.A.1.10 The Ferric Iron Uptake Transporter (FeT) Family

3.A.1.10.1

Ferric iron (Fe³⁺) porter

SfuABC of Serratia marcescens
SfuA (R)
SfuB (M)
SfuC (C)

3.A.1.10.2

Ferric iron (Fe³⁺) porter

Fut A1A2BC of SynechocystisPCC6803
FutA1 (R)
FutA2 (R)
FutB (M)
FutC (C)

3.A.1.10.3

Ferric iron (Fe³⁺) porter (selective for trivalent cations, Fe³⁺, Ga³⁺ and Al³⁺) (Anderson et al., 2004)

FbpABC (HitABC) of Haemophilus influenzae
FbpA (R) (AAC21773)
FbpB (M) (AAC21774)
FbpC (C) (AAC21775)

3.A.1.11 The Polyamine/Opine/Phosphonate Uptake Transporter (POPT) Family

3.A.1.11.1

Polyamine (putrescine/spermidine) porter

PotABCD of E. coli
PotA (C)
PotB (M)
PotC (M)
PotD (R)

3.A.1.11.2

Putrescine porter

PotGHIF of E. coli
PotG (C)
PotH (M)
PotI (M)
PotF (R)

3.A.1.11.3

Mannopine porter

MotABCD of Agrobacterium tumefaciens plasmid pTil5955
MotA (R)
MotB (C)
MotC (M)
MotD (M)

3.A.1.11.4

Chrysopine porter

ChtGHIJK of Agrobacterium tumefaciens
ChtG (C)
ChtH (R)
ChtI (R)
ChtJ (M)
ChtK (M)

3.A.1.11.5

2-aminoethyl phosphonate porter

PhnSTUV of Salmonella typhimurium
PhnS (R)
PhnT (C)
PhnU (C)
PhnV (M)

3.A.1.12 The Quaternary Amine Uptake Transporter (QAT) Family (Similar to 3.A.1.16 and 3.A.1.17)

3.A.1.12.1

Glycine betaine/proline porter (also transports proline betaine, carnitine, dimethyl proline, homobetaine, γ-butyrobetaine and choline with low affinity)

ProVWX of E. coli
ProW (M)
ProX (R)
ProV (C)

3.A.1.12.2

Glycine betaine porter (also transports dimethylsulfonioacetate and dimethylsulfoniopropionate)

OpuAA, AB, AC of Bacillus subtilis
OpuAA (C)
OpuAB (M)
OpuAC (R)

3.A.1.12.3

Choline porter

OpuBA, BB, BC, BD of Bacillus subtilis
OpuBA (C)
OpuBB (M)
OpuBC (R)
OpuBD (M)

3.A.1.12.4

Uptake system for choline, L-carnitine, D-carnitine, glycine betaine, proline betaine, crotonobetaine, γ-butyrobetaine, dimethylsulfonioacetate, dimethylsulfoniopropionate, ectoine and choline-O-sulfate

OpuCA, CB, CC, CD of Bacillus subtilis
OpuCA (C)
OpuCB (M)
OpuCC (R)
OpuCD (M)

3.A.1.12.5

Uptake system for glycine-betaine (high affinity) and proline (low affinity)

BusAA-AB
BusAA (C)
BusAB (M-R)

3.A.1.12.6

Uptake system for hisitidine, proline, proline-betaine and glycine-betaine

HutXWV of Sinorhizobium meliloti
HutX (R)
HutW (M)
HutV (C)

3.A.1.12.7

High affinity (3 μM) choline-specific uptake system (Dupont et al., 2004)

ChoXWV of Sinorhizobium meliloti
ChoX (R) (AAM00244)
ChoW (M) (AAM00245)
ChoV (C) (AAM00246)

3.A.1.13 The Vitamin B₁₂ Uptake Transporter (B₁₂T) Family (Similar to 3.A.1.14)

3.A.1.13.1

Vitamin B₁₂ porter

BtuECD of E. coli
BtuC (M)
BtuD (C)
BtuF (R)

3.A.1.14 The Iron Chelate Uptake Transporter (FeCT) Family (Similar to 3.A.1.13 and 3.A.1.15)

3.A.1.14.1

Iron (Fe³⁺) or ferric-dicitrate porter

FecBCDE of E. coli
FecB (R)
FecC (M)
FecD (M)
FecE (C)

3.A.1.14.2

Iron (Fe³⁺)-enterobactin porter

FepBCDG of E. coli
FepB (R)
FepC (C)
FepD (M)
FepG (M)

3.A.1.14.3

Iron (Fe³⁺)-hydroxamate (ferrichrome, coprogen, aerobactin, ferrioxamine B, schizakinen, rhodotorulic acid) porter, albomycin porter

FhuBCD of E. coli
FhuB (M)
FhuC (C)
FhuD (R)

3.A.1.14.4

Iron-chrysobactine porter

CbrABCD of Erwinia chrysanthemi
CbrA (R)
CbrB (M)
CbrC (M)
CbrD (C)

3.A.1.14.5

Heme (hemin) uptake porter

HmuTUV of Yersinia pestis
HmuT (R)
HmuU (M)
HmuV (C)

3.A.1.14.6

The iron-vibriobactin/enterobactin uptake porter

ViuPDGC of Vibrio cholerae
ViuP (R)
ViuD (M)
ViuG (M)
ViuC (C)

3.A.1.14.7

Iron (Fe³⁺)-hydroxamate porter (transports Fe³⁺-ferrichrome and Fe³⁺-ferrioxamine B with FhuD1, and these compounds plus aerobactin and coprogen with FhuD2).

FhuBCD1D2 of Staphylococcus aureus
FhuB (M)
FhuC (C)
FhuD1 (R)
FhuD2 (R)

3.A.1.14.8

The iron-vibrioferrin uptake porter (Tanabe et al., 2003)

PvuBCDE of Vibrio parahaemolyticus
PvuB (R) (BAC16540)
PvuC (M) (BAC16541)
PvuD (M) (BAC16542)
PvuE (C) (BAC16543)

3.A.1.15 The Manganese/Zinc/Iron Chelate Uptake Transporter (MZT) Family (Similar to 3.A.1.12 and 3.A.1.16)

3.A.1.15.1

Manganese (Mn²⁺) porter

MntABC of Synechocystis 6803
MntA (C)
MntB (M)
MntC (R)

3.A.1.15.2

Manganese (Mn²⁺) and zinc (Zn²⁺) porter

ScaABC of Streptococcus gordonii
ScaA (R)
ScaB (M)
ScaC (C)

3.A.1.15.3

Zinc (Zn²⁺) porter

AdcABC of Streptococcus pneumoniae
AdcA (R)
AdcB (M)
AdcC (C)

3.A.1.15.4

Iron and manganese porter

YfeABCD of Yersinis pestis
YfeA (R)
YfeB (C)
YfeC (M)
YfeD (M)

3.A.1.15.5

Zinc (Zn²⁺) porter

ZnuABC (YebLMI) of E. coli
ZnuA (R)
ZnuC (C)
ZnuB (M)

3.A.1.15.6

Iron (Fe²⁺)/Zinc (Zn²⁺)/Copper (Cu²⁺) porter

MtsABC of Streptococcus pyogenes
MtsA (R)
MtsB (C)
MtsC (M)

3.A.1.15.7

Manganese (Mn²⁺) (Km=0.1 μM) and iron (Fe²⁺) (5 μM) porter (inhibited by Cd²⁺ > Co²⁺ > Ni²⁺, Cu²⁺) (most similar to YfeABCD of Yersinia pestis (TC #3.A.1.15.4))

SitABCD of Salmonella typhimurium
SitA (R)
SitB (C)
SitC (M)
SitD (M)

3.A.1.15.8

Magnesium (Mg²⁺), zinc (Zn²⁺) and possibly iron (Fe²⁺) porter (Hazlett et al., 2003)

TroABCD of Treponema pallidum
TroA (R) P96116
TroB (C) P96117
TroC (M) P96118
TroC (M) P96119

3.A.1.16 The Nitrate/Nitrite/Cyanate Uptake Transporter (NitT) Family (Similar to 3.A.1.12 and 3.A.1.17)

3.A.1.16.1

Nitrate/nitrite porter

NrtABCD of Synechococcus sp. (PCC 7942)
NrtA (R)
NrtB (M)
NrtC (C)
NrtD (C)

3.A.1.16.2

Cyanate porter

CynABD of Synechococcus PCC7942
CynA (R)
CynB (M)
CynD (C)

3.A.1.16.3

Bicarbonate porter

CmpABCD of Synechococcus sp.
CmpA (R)
CmpB (M)
CmpC (C)
CmpD (C)

3.A.1.17 The Taurine Uptake Transporter (TauT) Family (Similar to 3.A.1.12 and 3.A.1.16)

3.A.1.17.1

Taurine (2-aminoethane sulfonate) porter

TauABC of E. coli
TauA (R)
TauB (C)
TauC (M)

3.A.1.17.2

Aromatic sulfonate porter

SsuABC of Pseudomonas putida
SsuA (R)
SsuB (C)
SsuC (M)

3.A.1.18 The Putative Cobalt Uptake Transporter (CoT) Family

3.A.1.18.1

Cobalt (Co²⁺) porter (probable)

CbiNOQ of Salmonella typhimurium
CbiN (R)
CbiO (C)
CbiQ (M)

3.A.1.19 The Thiamin Uptake Transporter (ThiT) Family (Most similar to 3.A.1.10, 3.A.1.6 and 3.A.1.8 in that order)

3.A.1.19.1

Thiamin; thiamin pyrophosphate porter

ThiBPQ of Salmonella typhimurium (functionally characterized and partially sequenced) and E. coli (fully sequenced but not functionally characterized)
ThiB; TbpA (R)
ThiP; YabK (M)
ThiQ; YabJ (C)

3.A.1.20 The Brachyspira Iron Transporter (BIT) Family (Most similar to 3.A.1.6, 3.A.1.8 and 3.A.1.11)

3.A.1.20.1

The iron transporter, BitABCDEF

BitABCDEF of Brachyspira (Serpulina) hyodysenteriae
BitA (R)
BitB (R)
BitC (R)
BitD (C)
BitE (M)
BitF (M)

3.A.1.21 The (Putative) Yersiniabactin Fe³⁺ Uptake Transporter(s) (YbtPQ) Family (YbtP and YbtQ resemble ABC exporters of Streptomyces species)

3.A.1.21.1

YbtP, YbtQ

YbtPQ of Yersinia pestis
YbtP (M-C)
YbtQ (M-C)

3.A.1.22 The Nickel Uptake Transporter (NiT) Family

3.A.1.22.1

Nickel (Ni²⁺) porter

CbiKMQO of Actinobacillus pleuropneumoniae
CbiK (R)
CbiM (M)
CbiQ (M)
CbiO (C)

3.A.1.23 The Nickel/Cobalt Uptake Transporter (NiCoT) Family

3.A.1.23.1

Nickel (Ni²⁺) porter (Chen and Burne, 2003)

UreMQO of Streptococcus salivarius
UreM (M) (AAQ81894)
UreQ (M) (AAQ81895)
UreO (C) (AAQ81896)
UreK (R) (Unknown)

3.A.1.23.2

Putative cobalt (Co²⁺) porter (Chen and Burne, 2003)

CbiMQOK of Clostridium acetobutylicum
CbiM (M) (AAK79333)
CbiQ (M) (AAK79335)
CbiO (C) (AAK79336)
CbiK (R?) (AAK79334)

3.A.1.24 The Methionine Uptake Transporter (MUT) Family (Similar to 3.A.1.3 and 3.A.1.12)

3.A.1.24.1

The L- and D-methionine porter (also transports formyl-L-methionine) (Zhang et al., 2003)

MetNIQ (abc-yaeE-yaeC) of E. coli
MetN (C) AAC73310
MetI (M) AAC73309
MetQ (R) AAC73308

3.A.1.24.2

The L- and D-methionine porter (also transports methionine sulfoxide (Hullo et al., 2004)

MetNPQ (YusCBA) of Bacillus subtilis
MetN (C) CAB15264
MetP (M) CAB15263
MetQ (R) CAB15262

3.A.1.101 The Capsular Polysaccharide Exporter (CPSE) Family

3.A.1.101.1

Capsular polysaccharide exporter

Gram-negative bacteria

KpsMT of E. coli KpsM
KpsM (M)
KpsT (C)

3.A.1.102 The Lipooligosaccharide Exporter (LOSE) Family

3.A.1.102.1

Lipooligosaccharide exporter (nodulation proteins, NodIJ)

Gram-negative bacteria

NodIJ of Rhizobium galegae
NodJ (M)
NodI (C)

3.A.1.103 The Lipopolysaccharide Exporter (LPSE) Family

3.A.1.103.1

Lipopolysaccharide exporter

Gram-negative bacteria

RfbAB of Klebsiella pneumoniae
RfbA (M)
RfbB (C)

3.A.1.103.2

Heteropolysaccharide O-antigen exporter (Feng et al., 2004)

Gram-negative bacteria

Wzm/Wzt of E. coli
Wzm (M) (AAS99164)
Wzt (C) (AAS99165)

3.A.1.104 The Teichoic Acid Exporter (TAE) Family

3.A.1.104.1

Teichoic acid exporter

Gram-positive bacteria

TagGH of Bacillus subtilis
TagG (M)
TagH (C)

3.A.1.105 The Drug Exporter-1 (DrugE1) Family

3.A.1.105.1

Daunorubicin; doxorubicin (drug resistance) exporter

Gram-positive bacteria

DrrAB of Streptomyces peucetius
DrrA (C)
DrrB (M)

3.A.1.105.2

Oleandomycin (drug resistance) exporter

Gram-positive bacteria

OleC4-OleC5 of Streptomyces antibioticus
OleC4 (C)
OleC5 (M)

3.A.1.106 The Lipid Exporter (LipidE) Family

3.A.1.106.1

Phospholipid, LPS, lipid A and drug exporter (flippase), MsbA (essential for export to the outer membrane). MsbA also confers drug resistance to azidopine, daunomycin, vinblastine, Hoechst 33342 and ethidium (Reuter et al., 2003).

Gram-negative bacteria

MsbA (M-C) of E. coli

3.A.1.107 The Putative Heme Exporter (HemeE) Family

3.A.1.107.1

Putative heme exporter, CcmABC=CycVWZ (Note: CcmC may function independently of CcmAB)

Gram-negative bacteria

CycVWZ of Bradyrhizobium japonicum
CycV (C)
CycW (M)
CycZ (M)

3.A.1.108 The β-Glucan Exporter (GlucanE) Family

3.A.1.108.1

β-Glucan exporter

Gram-negative bacteria

NdvA (M-C) of Rhizobium meliloti

3.A.1.109 The Protein-1 Exporter (Prot1E) Family

3.A.1.109.1

α-Hemolysin exporter

Gram-negative bacteria

HlyB (M-C) of E. coli

3.A.1.109.2

Cyclolysin exporter

Gram-negative bacteria

CyaB (M-C) of Bordetella pertussis

3.A.1.109.3

LapA adhesin protein exporter, LapB (Hinsa et al., 2003)

Bacteria

LapB of Pseudomonas putida
LapB (MC) (AAN65800)

3.A.1.110 The Protein-2 Exporter (Prot2E) Family

3.A.1.110.2

Colicin V exporter

Enteric bacteria

CvaB (M-C) of E. coli

3.A.1.110.3

Multiple protein exporter

Gram-negative bacteria

PrsD (M-C) of Rhizobium leguminosarum

3.A.1.110.4

Alkaline protease exporter

Gram-negative bacteria

AprD (M-C) of Pseudomonas aeruginosa

3.A.1.110.5

S-layer protein exporter

Gram-negative bacteria

RsaD (M-C) of Caulobacter crescentus

3.A.1.110.6

Exporter for lipase, LipA, protease, PrtA and S-layer protein SlaA

Gram-negative bacteria

LipB (M-C) of Serratia marcescens

3.A.1.110.7

Exporter for heme-binding protein and metaloprotease

Gram-negative bacteria

HasD (M-C) of Serratia marcescens

3.A.1.110.8

Surface layer protein exporter

Gram-negative bacteria

SapD (M-C) of Campylobacter fetus

3.A.1.110.9

Exporter of HasA lipase, and alkaline protease

Gram-negative bacteria

HasD (M-C) of Pseudomonas fluorescens

3.A.1.111 The Peptide-1 Exporter (Pep1E) Family

3.A.1.111.1

Hemolysin/bacteriocin (cytolysin) exporter with associated proteolytic activity

Gram-positive bacteria

CylT (M-C) (CylB) of Enterococcus faecalis

3.A.1.111.2

Subtilin (toxic peptide) exporter

Gram-positive bacteria

SpaB (M-C) of Bacillus subtilis

3.A.1.111.3

Nisin exporter

Gram-positive bacteria

NisT (M-C) of Lactococcus lactis

3.A.1.112 The Peptide-2 Exporter (Pep2E) Family

3.A.1.112.1

Competence factor (CSF; a heptadecapeptide) exporter

Gram-positive bacteria

ComA (M-C) of Streptococcus pneumoniae (functions with putative MFP accessory protein, ComB)

3.A.1.112.2

Pediocin PA-1 exporter

Gram-positive bacteria

PedD (M-C) of Pediococcus acidilactici

3.A.1.112.3

Bacteriocin (lactococcin) exporter

Gram-positive bacteria

LcnC (M-C) of Lactococcus lactis (functions with putative MFP accessory protein LcnD)

3.A.1.112.4

Sublancin exporter, SunT

Gram-positive bacteria

SunT (M-C) of Bacillus subtilis

3.A.1.113 The Peptide-3 Exporter (Pep3E) Family

3.A.1.113.1

Modified cyclic peptide (syringomycin) exporter, SyrD

Gram-negative bacteria

SyrD (M-C) of Pseudomonas syringae

3.A.1.113.2

Pyoverdin (siderophore) exporter

Gram-negative bacteria

PvdE (M-C) of Pseudomonas aeruginosa

3.A.1.114 The Probable Glycolipid Exporter (DevE) Family

3.A.1.114.1

Probable glycolipid exporter (under nitrogen control in heterocysts)

Cyanobacteria

DevAC of Anabaena variabilis (sp. strain PCC7120)
DevA (C)
DevC (M)

3.A.1.115 The Na⁺ Exporter (NatE) Family

3.A.1.115.1

Na⁺ efflux pump NatAB

Gram-positive bacteria

NatAB of Bacillus subtilis
NatA (M)
NatB (C)

3.A.1.116 The Microcin B17 Exporter (McbE) Family

3.A.1.116.1

Microcin B17 exporter

Enteric bacteria

McbEF of E. coli
McbE (M)
McbF (C)

3.A.1.117 The Drug Exporter-2 (DrugE2) Family

3.A.1.117.1

The multidrug exporter, LmrA (can also substitute for MsbA [TC #3.A.1.106.1] to export lipid A; Reuter et al., 2003).

Gram-positive bacteria

LmrA (M-C) of Lactococcus lactis

3.A.1.117.2

Hop resistance protein, HorA

Gram-positive bacteria

HorA (M-C) of Lactobacillus brevis

3.A.1.118 The Microcin J25 Exporter (McjD) Family

3.A.1.118.1

The cyclic peptide antibiotic, microcin J25 exporter, McjD

Gram-negative bacteria

McjD (M-C) of E. coli

3.A.1.119 The Drug/Siderophore Exporter-3 (DrugE3) Family

3.A.1.119.1

5-Hydroxystreptomycin and other streptomycin-like aminoglycoside exporter, StrVW

Gram-positive bacteria

StrVW of Streptomyces glaucescens
StrV (M-C)
StrW (M-C)

3.A.1.119.2

Tetracycline/oxytetracycline/oxacillin exporter, TetAB

Gram-positive bacteria

TetAB (StrAB) of Corynebacterium striatum
TetA (M-C)
TetB (M-C)

3.A.1.119.3

Exochelin exporter, ExiT

Gram-positive bacteria

ExiT of Mycobacterium smegmatis
(MC-M-C)

3.A.1.120 The (Putative) Drug Resistance ATPase-1 (Drug RA1) Family

3.A.1.120.1

Macrolide ATPase (membrane constituent unknown)

Gram-positive bacteria

SrmB (C-C) of Streptomyces ambofaciens

3.A.1.120.2

Tylosin ATPase (membrane constituent unknown)

Gram-positive bacteria

TlrC (C-C) of Streptomyces fradiae

3.A.1.120.3

Oleandomycin resistance ATPase (membrane constituent unknown)

Gram-positive bacteria

OleB (C-C) of Streptomyces antibioticus

3.A.1.120.4

Carbomycin resistance ATPase (membrane constituent unknown)

Gram-positive bacteria

Carbomycin, CarA (C-C), protein of Streptomyces thermtolerans

3.A.1.121 The (Putative) Drug Resistance ATPase-2 (Drug RA2) Family

3.A.1.121.1

Erythromycin ATPase (membrane constituent unknown)

Gram-positive bacteria

MsrA (C-C) of Staphylococcus epidermidis

3.A.1.121.2

Pristinamycin resistance protein, VgaG

Gram-positive bacteria

VgaB (C-C) of Staphylococcus aureus

3.A.1.122 The Macrolide Exporter (MacB) Family

3.A.1.122.1

Macrolide (14- and 15- but not 16-membered lactone macrolides including erythromycin) exporter, MacB

Gram-negative bacteria

MacB (C-C) of E. coli

3.A.1.123 The Peptide-4 Exporter (Pep4E) Family

3.A.1.123.1

Pep5 lantibiotic exporter, PepT

Gram-positive bacteria

PepT (M-C) of Staphylococcus epidermis

3.A.1.123.2

Aureocin A70 multipeptide bacteriocin (AurA, AurB, AurC, AurD) exporter, AurT

Gram-positive bacteria

AurT (M-C) of Staphylococcus aureus

3.A.1.123.3

The lantibiotic, salivericin A exporter, SalXY

Gram-positive bacteria

SalXY of Streptococcus salivarius
SalX (C)
SalY (M)

3.A.1.123.4

The bacitracin-resistance (putative bacitracin exporter), MbrAB

Gram-positive bacteria

MbrAB of Streptococcus mutans
MbrA (C)
MbrB (M)

3.A.1.123.5

The bacitracin exporter, BceAB (Ohki et al., 2003)

Gram-positive bacteria

BceAB (YtsCD) of Bacillus subtilis
BceA (C) CAB15016
BceB (M) CAB15015

3.A.1.124 The 3-component Peptide-5 Exporter (Pep5E) Family

3.A.1.124.1

The 3-component nisin immunity exporter, NisFEG

Gram-positive bacteria

NisFEG of Lactococcus lactis
NisF (C)
NisE (M)
NisG (M)

3.A.1.124.2

The 3-component subtilin immunity exporter, SpaEFG

Gram-positive bacteria

SpaEFG of Bacillus subtilis
SpaE (M)
SpaF (C)
SpaG (M)

3.A.1.125 The Lipoprotein Translocase (LPT) Family

3.A.1.125.1

Lipoprotein translocation system (translocates lipoproteins from the inner membrane to periplasmic chaperone, LolA, which transfers the lipoproteins to an outer membrane receptor, LolB, which anchors the lipoprotein to the outer membrane of the Gram-negative bacterial cell envelope) (Narita et al., 2003)

Gram-negative bacteria

LolCDE of E. coli
LolC (M)
LolD (C)
LolE (M)

3.A.1.126 The β-Exotoxin I Exporter (βETE) Family

3.A.1.126.1

Exporter of β-exotoxin I, BerAB

Bacteria

β-exotoxin exporter, BerAB, of Bacillus thuringiensis
BerA (C)
BerB (M)

3.A.1.127 The AmfS Peptide Exporter (AmfS-E) Family

3.A.1.127.1

Exporter of AmfS extracellular peptidic morphogen (Chater and Horinouchi, 2003; Ueda et al., 2002)

Bacteria

AmfS exporter, AmfAB of Streptomyces griseus
AmfA (MC) (BAA33537)
AmfB (MC) (BBA33538)

3.A.1.128 The SkfA Peptide Exporter (SkfA-E) Family

3.A.1.128.1

Exporter of SkfA processed peptide (spO31422), SkfEF (González-Pastor et al., 2003)

Bacteria

SkfEF (YbdAB) of Bacillus subtilis
SkfE (C) O31427
SkfF (M) O31438

3.A.1.201 The Multidrug Resistance Exporter (MDR) Family (ABCB)

3.A.1.201.1

Broad specificity multidrug resistance (MDR) efflux pump (exports amphiphilic compounds of unrelated chemical structure); peptide efflux pump; phospholipid (e.g., phosphatidyl serine), cholesterol and sterol flippase (also called ABCB1 and p-gp))

Animals, fungi, bacteria

MDR1 of Homo sapiens

3.A.1.201.2

Bile salt export pump, BSEP or SPGP (associated with progressive familial intrahepatic cholestasis-2) (also called ABCB11)

Animals

BSEP of Homo sapiens

3.A.1.201.3

Short chain fatty acid phosphatidylcholine translocase, MDR3 (associated with progressive familial intrahepatic cholestasis-3). (Narrow drug specificity relative to MDR1. Exports digoxin, paclitaxel, vinblastin and bile acids.) (also called ABCB4)

Animals

MDR3 of Homo sapiens

3.A.1.201.4

The multidrug resistance/chloroquine resistance protein, Pfmdr1

Protozoa

Pfmdr1 of Plasmodium falciparum (P13568)

3.A.1.202 The Cystic Fibrosis Transmembrane Conductance Exporter (CFTR) Family (ABCC)

3.A.1.202.1

Cystic fibrosis transmembrane conductance regulator (CFTR)(also called ABCC7); cyclic AMP-dependent chloride channel; also catalyzes nucleotide (ATP-ADP)-dependent glutathione flux (Kogan et al., 2003) (may also activate inward rectifying K⁺ channels)

Animals

CFTR of Homo sapiens

3.A.1.203 The Peroxysomal Fatty Acyl CoA Transporter (P-FAT) Family (ABCD)

3.A.1.203.1

Peroxysomal long chain fatty acyl (LCFA) transporter associated with Zellweger Syndrome

Animals

PMP70 of Homo sapiens

3.A.1.203.2

Peroxysomal long chain fatty acyl (LCFA) Coenzyme A import porter

Yeast

Pat1 (758-870 aas; 5 TMSs)/Pat2 (853 aas; 4 TMSs) of Saccharomyces cerevisiae

3.A.1.203.3

Long chain fatty acid (LCFA) transporter, ABCD1 (ALD, the adrenoleukodystrophy protein)

Animals

LCFA transporter of Homo sapiens

3.A.1.204 The Eye Pigment Precursor Transporter (EPP) Family (ABCG)

3.A.1.204.1

Eye pigment precursor transporter

Animals, yeast

White of Drosophila melanogaster

3.A.1.204.2

Drug resistance transporter, ABCG2 (MXR; ABCP) (human breast cancer resistance protein) (also transports sterols: estradiol, and probably cholesterol, progesterone, testosterone and tamoxifen) (Janvilisri et al., 2003). It is a homotetramer (Xu et al., 2004).

Animals, yeast

ABCG2 (ABCP) of Homo sapiens

3.A.1.204.3

Breast cancer resistance protein, BCRP (ABCG) (MDR pump) (exports from human breast cancer cell line MCF-7: miloxantrone, daunorubicin, doxorubicin and rhodamine123)

Animals

BCRP of Homo sapiens (AAC97367)

3.A.1.205 The Pleiotropic Drug Resistance (PDR) Family (ABCG)

3.A.1.205.1

Pleiotropic drug resistance (PDR) exporter; steroid exporter; sporidesmin toxicity suppressor (Sts1); MDR; cyclic nucleotide exporter; amphipathic anion exporter

Yeast

Pdr5 (Sts1; Ydr1) of Saccharomyces cerevisiae

3.A.1.205.2

Drug/Sterol/Mutagen exporter, Snq2p

Yeast

Snq2p of Saccharomyces cerevisiae

3.A.1.205.3

Weak acid exporter, Pdr12p

Yeast

Pdr12p of Saccharomyces cerevisiae

3.A.1.205.4

Multidrug resistance protein, Cdr1 (confers resistance to cycloheximide and antifungal agents such as azoles and terbinafine) (Schuetzer-Muehlbauer et al., 2003)

Yeast

Cdr1 of Candida albicans

3.A.1.205.5

Multidrug resistance protein, Cdr2 (confers resistance to azole and other antifungal agents/terbinafine, amorolfine, aspofungin, etc. as well as a variety of metabolic inhibitors) (Schuetzer-Muehlbauer et al., 2003)

Yeast

Cdr2 of Candida albicans

3.A.1.205.6

Multidrug resistance protein, CnAFR1 (confers resistance to azole antifungal drugs including fluconazole) (Posteraro et al., 2003)

Fungi

CnAFR1 of Cryptococcus neoformans

3.A.1.205.7

The multidrug resistance protein, AtrB (confers resistance to all major classes of fungicides as well as natural toxic compounds substrates include: anilinopyrimidine, benzimidazole, phenylpyrrole, phenylpyridylamine, strobirulin, azoles, dicarboximides, quintozene, acriflavin, and rhodamine 6G as well as natural toxins such as camptothecin (an alkaloid) and the stilbene phytoalexin, resveratrol) (Andrade et al., 2000).

Fungi

AtrB of Aspergillus nidulans

3.A.1.206 The a-Factor Sex Pheromone Exporter (STE) Family (ABCB)

3.A.1.206.1

a-Factor sex pheromone exporter (Ste6)

Yeast

Ste6 of Saccharomyces cerevisiae

3.A.1.208 The Conjugate Transporter Family (ABCC)

3.A.1.208.1

Multi-drug resistance-associated protein, MRP1-like protein (MLP1 or MRP1) (Exporter of leukotrienes, glutathione and cysteinyl conjugates of organic anions, drugs, unmodified hydrophobic xenobiotics and hydrophilic conjugated endobiotics). Vincristine and glutathione are co-transported.

Animals

MRP1 of Rattus norvegicus

3.A.1.208.2

Hepatic canalicular conjugate exporter (the Dubin-Johnson Syndrome protein) (transports bilirubin glucuronides; dianionic bile salts such as taurocholate, taurochenodeoxycholate sulfate and taurolithocholate sulfate; glutathione; glutathione conjugates; cysteinyl leukotrienes; arsenic-glutathione complexes and glutathione disulfide) (also called ABCC2)

Animals

cMRP (MRP2; cMOAT) of Homo sapiens

3.A.1.208.3

Oligomycin-resistance protein YOR1 in plasma membrane

Yeast

YOR1 of Saccharomyces cerevisiae

3.A.1.208.4

SUR1 sulfonylurea receptor; subunit and regulator of α-cell ATP-sensitive K⁺ channel (TC #1.A.2); determines ATP sensitivity; no inherent transport function known; associated with persistent hyperinsulinemic hypoglycemia of infancy due to focal adenomatous hyperplasia (also called ABCC8)

Animals

SUR1 of Homo sapiens

3.A.1.208.5

Vacuolar multidrug resistance efflux pump, AtMRP2 (catalyzes vacuolar uptake of glutathione conjugates (i.e., 2,4-dinitrophenyl-GS), glucuronide conjugates (i.e., 17 β-estradiol 17(β-D-glucuronide), and reduced glutathione)

Plants

AtMRP2 of Arabidopsis thaliana

3.A.1.208.6

Metal-thiol conjugate exporter, PgpA; glutathione and trypanothione conjugates are exported; confers arsenite and antimonite resistance (trypanothione is glutathione-spermidine).

Protozoa

PgpA of Leishmania tarentolae

3.A.1.208.7

MRP4 (exporter of cyclic nucleotides (cAMP, cGMP), purine analogues, methotrexate, prostaglandins, reduced folates, 9(2-phosphonylmethyoxy-
ethyl)adenine and estradiol 17-β-D-glucuronide) (inhibited by nonsteroidal antiinflammatory drugs (Reid et al., 2003))

Animals

MRP4 (MOAT-B) of Homo sapiens

3.A.1.208.8

Drug resistance pump; ABCC1 (MRP1), exports chemotherapeutic agents, organic anions such as leukotriene C₄, 17-β-
estradiol 17-β-D-glucuronide), estrone-3-sulfate, methotrexate, arsenic triglutathione and glutathione. Changing charged residues in TMS6 (K332, H335 and D336) gave rise to specific changes in specificity (Haimeur et al., 2002; Leslie et al., 2004)

Animals

MRP1 of Homo sapiens

3.A.1.208.9

Canicular multispecific organic anion transporter, MRP3 (also called ABCC3) (most similar in sequence to MRP2). MRP3 exports epipodophyllotoxins, etoposide and teniposide, estradiol 17-β-
D-glucuronide, leukotriene C₄, dinitrophenyl S-glutathione, epoposide glucuronide, and possibly methotrexate.

Animals

MRP3 of Homo sapiens

3.A.1.208.10

Multidrug (anthracycline) resistance organic anion efflux pump (ABC-C6; MRP6; MOAT-E - the pseudoxanthoma elasticum disease protein) exports glutathione conjugates including lencotriene C₄ and N-ethylmaleimide S-glutathione and probably exports probenecid, benzbromarone and indomethacin.

Animals

ABCC6 (MRP6) of Homo sapiens

3.A.1.208.11

Vacuolar metal resistance and drug detoxification protein, yeast cadmium factor (YCF1); transports cadmium-
glutathione conjugates, glutathione S-conjugated leucotriene C₄, organic glutathione S-conjugates, unconjugated bilirubin and reduced glutathione

Yeast

YCF1 of Saccharomyces cerevisiae

3.A.1.208.12

Bile acid transporter, BAT1 (in vacuoles)

Yeast

BAT1 of Saccharomyces cerevisiae

3.A.1.208.13

Cyclic nucleotide (cAMP and cGMP) efflux pump, MRP8 (ABCC11); also confers resistance to fluoropyrimidines and the anti-AIDS drug, 2',3'-dideoxycytidine (Guo et al., 2003)

Animals

MRP8 (ABCC11) of Homo sapiens (NP_115972)

3.A.1.209 The MHC Peptide Transporter (TAP) Family (ABCB)

3.A.1.209.1

MHC heterodimeric peptide exporter (TAP) (from cytoplasm to the endoplasmic reticulum) (TAP1=ABCB2; TAP2=ABCB3) (defects in TAP1 or TAP2 cause immunodeficiency) (TAP1/TAP2 is stabilized by tapasin isoforms 1, 2 and 3) (Raghuraman et al., 2002)

Animals, yeast

TAP1/TAP2 of Homo sapiens

3.A.1.210 The Heavy Metal Transporter (HMT) Family (ABCB)

3.A.1.210.1

The putative mitochondrial iron transporter, ATM1 (possibly specific for iron-sulfur clusters)