TCDB is operated by the Saier Lab Bioinformatics Group

2.A.12 The ATP:ADP Antiporter (AAA) Family

Members of the AAA family have been sequenced from bacteria and plants (Winkler and Neuhaus, 1999). One protein from the obligate intracellular bacterial parasite, Rickettsia prowazekii, the etiologic agent of the human disease epidemic typhus, is of 498 amino acyl residues and is believed to span the membrane 12 times (Alexeyev et al., 1999). The transporter is an obligate exchange translocase specific for ATP and ADP. It functions to take up ATP from the eukaryotic cell cytoplasm into the bacterium in exchange for ADP. The bacteria thus gains energy in the form of one pyrophosphate bond per ATP molecule taken up. Five AAA family paralogues are encoded within the genome of R. prowazekii. This organism transports UMP and GMP but not CMP, and it seems likely that one or more of the AAA family paralogues are responsible. Many other species of Rickettsia also possess AAA family homologues (Alexeyev et al., 1999). The ATP/ADP uniporters can also transport inorganic phosphate (Trentmann et al., 2008).

The AAA family proteins may be distantly related to members of the major facilitator superfamily (MFS; TC #2.A.1) and are not related to the mitochondrial ATP/ADP exchangers of the Mitochondrial Carrier Family (MCF; TC #2.A.5) which pump ATP out of mitochondria in accordance with the polarity of the mitochondrial membrane potential. However, two homologous adenylate translocators of the plant, Arabidopsis thaliana, have been sequenced and characterized. They are reported to be 589 and 569 amino acyl residues in length, possess twelve putative transmembrane spanners, and are about 85% identical to each other. They are about 44% identical to the rickettsial translocator described above. They are postulated to be localized to the intracellular plastid membrane where they function as ATP importers (Kampfenkel et al., 1995).

The genome of Chlamydia trachomatis encodes two AAA family members termed nucleoside-phosphate transporters 1 and 2, Npt1 and Npt2. They exhibit 68% and 61% similarity to the characterized R. prowazekii ATP:ADP antiporter. They similarly exhibit 12 putative TMSs. When expressed in E. coli, Npt1 catalyzed ATP:ADP exchange with KM values of 48 (ATP) and 30 (ADP) μM. No other nucleotides including AMP, GTP, dATP, CTP and UTP were transported. Ntp2 transported all four ribonucleoside triphosphates with KM values of 30 μM (GTP), 300 μM (UTP), 500 μM (CTP) and 1200 μM (ATP), probably employing a proton symport mechanism. Ribonucleoside di- and monophosphates as well as deoxyribonucleotides were not substrates (Tjaden et al., 1999).

The transport reaction catalyzed by the antiporters is:

ATP (out) + ADP (in) (+ energy?) ⇌ ATP (in) + ADP (out)

The transport reaction catalyzed by the proton symporter is probably:

NTP (out) + nH+ (out) → NTP (in) + nH+ (in)

This family belongs to the: MFS Superfamily.

References associated with 2.A.12 family:

Alexeyev, M.F. and H.H. Winkler. (1999). Membrane topology of the Rickettsia prowazekii ATP/ADP translocase revealed by novel dual pho-lac reporters. J. Mol. Biol. 285: 1503-1513. 9917392
Audia, J.P., and Winkler H.H. (2006). Study of the five Rickettsia prowazekii proteins annotated as ATP/ADP translocases (Tlc): Only Tlc1 transports ATP/ADP, while Tlc4 and Tlc5 transport other ribonucleotides. J. Bacteriol. 188: 6261-6268. 16923893
Conrath, U., C. Linke, W. Jeblick, P. Geigenberger, W.P. Quick, and H.E. Neuhaus. (2003). Enhanced resistance to Phytophthora infestans and Alternaria solani in leaves and tubers, respectively, of potato plants with decreased activity of the plastidic ATP/ADP transporter. Planta 217: 75-83. 12721851
Daugherty, R.M., N. Linka, J.P. Audia, C. Urbany, H.E. Neuhaus, and H.H. Winkler. (2004). The nucleotide transporter of Caedibacter caryophilus exhibits an extended substrate spectrum compared to the analogous ATP/ADP translocase of Rickettsia prowazekii. J. Bacteriol. 186: 3262-3265. 15126491
Fisher, D.J., R.E. Fernández, and A.T. Maurelli. (2013). Chlamydia trachomatis Transports NAD via the Npt1 ATP/ADP Translocase. J. Bacteriol. 195: 3381-3386. 23708130
Haferkamp, I., S. Schmitz-Esser, M. Wagner, N. Neigel, M. Horn, and H.E. Neuhaus. (2006). Tapping the nucleotide pool of the host: novel nucleotide carrier proteins of Protochlamydia amoebophila. Mol. Microbiol. 60: 1534-1545. 16796686
Kampfenkel, K., T. Möhlmann, O. Batz, M.V. Montagu, D. Inze, and H.E. Neuhaus. (1995). Molecular characterization of an Arabidopsis thaliana cDNA encoding a novel putative adenylate translocator of higher plants. FEBS Lett. 374: 351-355. 7589569
Linke, C., U. Conrath, W. Jeblick, T. Betsche, A. Mahn, K. Düring, and H.E. Neuhaus. (2002). Inhibition of the plastidic ATP/ADP transporter protein primes potato tubers for augmented elicitation of defense responses and enhances their resistance against Erwinia carotovora. Plant Physiol. 129: 1607-1615. 12177473
Möhlmann, T., J. Tjaden, C. Schwöppe, H.H. Winkler, K. Kampfenkel, and H.E. Neuhaus. (1998). Occurrence of two plastidic ATP/ADP transporters in Arabidopsis thaliana L.--molecular characterisation and comparative structural analysis of similar ATP/ADP translocators from plastids and Rickettsia prowazekii. Eur J Biochem 252: 353-359. 9546649
Neuhaus, H.E., E. Thom, T. Möhlmann, M. Steup, and K. Kampfenkel. (1997). Characterization of a novel eukaryotic ATP/ADP translocator located in the plastid envelope of Arabidopsis thaliana L. Plant J. 11: 73-82. 9025303
Plano, G.V. and H.H. Winkler. (1991). Identification and initial topological analysis of the Rickettsia prowazekii ATP/ADP translocase. J. Bacteriol. 173: 3389-3396 1904433
Schmitz-Esser, S., I. Haferkamp, S. Knab, T. Penz, M. Ast, C. Kohl, M. Wagner, and M. Horn. (2008). Lawsonia intracellularis contains a gene encoding a functional rickettsia-like ATP/ADP translocase for host exploitation. J. Bacteriol. 190: 5746-5752. 18606736
Tjaden, J., H.H. Winkler, C. Schwöppe, M. Van Der Laan, T. Möhlmann, and H.E. Neuhaus. (1999). Two nucleotide transport proteins in Chlamydia trachomatis, one for net nucleoside triphosphate uptake and the other for transport of energy. J. Bacteriol. 181: 1196-1202. 9973346
Trentmann, O., B. Jung, H.E. Neuhaus, and I. Haferkamp. (2008). Nonmitochondrial ATP/ADP transporters accept phosphate as third substrate. J. Biol. Chem. 283: 36486-36493. 19001371
Trentmann, O., M. Horn, A.C. van Scheltinga, H.E. Neuhaus, and I. Haferkamp. (2007). Enlightening energy parasitism by analysis of an ATP/ADP transporter from chlamydiae. PLoS. Biol 5: e231. 17760504
Tsaousis, A.D., E.R. Kunji, A.V. Goldberg, J.M. Lucocq, R.P. Hirt, and T.M. Embley. (2008). A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi. Nature 453: 553-556. 18449191
Vahling, C.M., Y. Duan, and H. Lin. (2010). Characterization of an ATP translocase identified in the destructive plant pathogen "Candidatus Liberibacter asiaticus". J. Bacteriol. 192: 834-840. 19948801
Williamson, L.R., G.V. Plano, H.H. Winkler, D.C. Krause, and D.O. Wood. (1989). Nucleotide sequence of the Rickettsia prowazekii ATP/ADP translocase-encoding gene. Gene 80: 260-278. 2555259
Winkler, H.H. (1976). Rickettsial permeability. An ADP-ATP transport system. J. Biol. Chem. 251: 389-396.
Winkler, H.H. and H.E. Neuhaus. (1999). Non-mitochondrial ATP transport. Trends Biol. Sci. 24: 64-68. 10098400
Winkler, H.H., R. Daugherty, and F. Hu. (1999). Rickettsia prowazekii transports UMP and GMP, but not CMP, as building blocks for RNA synthesis. J. Bacteriol. 181: 3238-3241. 10322027