Genomes and Genes
nucleobase transport proteins
Summary: Proteins involved in the transport of nucleobases such as PYRIMIDINES and PURINES across membranes.
- Sanchez M, Tryon R, Pierce S, Vasudevan G, Landfear S. Functional expression and characterization of a purine nucleobase transporter gene from Leishmania major. Mol Membr Biol. 2004;21:11-8 pubmed..5, 8.5 +/- 0.6, 8.5 +/- 1.1, and 8.8 +/- 4.0 microM, respectively. LmaNT3 is, thus, the first member of the ENT family identified in any organism that functions as a nucleobase rather than nucleoside or nucleoside/nucleobase transporter. ..
- Kato R, Maeda T, Akaike T, Tamai I. Characterization of nucleobase transport by mouse Sertoli cell line TM4. Biol Pharm Bull. 2009;32:450-5 pubmed..These results suggested that there are distinct transport systems for purine and pyrimidine nucleobases in cells of mouse Sertoli cell line TM4. ..
- Qi Z, Xiong L. Characterization of a purine permease family gene OsPUP7 involved in growth and development control in rice. J Integr Plant Biol. 2013;55:1119-35 pubmed publisher..Our results indicate that the PUP transport system also exists in rice, and OsPUP7 has an important role in the transport of CK, thus affecting developmental process and stress responses. ..
- Ball M, Raynal A, Guerineau M, Iborra F. Construction of efficient centromeric, multicopy and expression vectors for the yeast Kluyveromyces marxianus using homologous elements and the promoter of a purine-cytosine-like permease. J Mol Microbiol Biotechnol. 1999;1:347-53 pubmed..This promoter appears to be constitutive in various conditions tested. Its five transcription start sites have been mapped, and a derivative expression vector for K. marxianus has been constructed. ..
- Al Salabi M, Wallace L, de Koning H. A Leishmania major nucleobase transporter responsible for allopurinol uptake is a functional homolog of the Trypanosoma brucei H2 transporter. Mol Pharmacol. 2003;63:814-20 pubmed..It is proposed that the architecture of their respective binding sites is very similar and that LmNBT1 can be named a functional homolog of TbH2. ..
- Szydlowski N, Bürkle L, Pourcel L, Moulin M, Stolz J, Fitzpatrick T. Recycling of pyridoxine (vitamin B6) by PUP1 in Arabidopsis. Plant J. 2013;75:40-52 pubmed publisher..Furthermore, combining the pup1 mutant with a vitamin B6 de novo biosynthesis mutant (pdx1.3) corroborates that PUP1 is involved in the uptake of the vitamin. ..
- Dessen P, Kepes F. The PAUSE software for analysis of translational control over protein targeting: application to E. nidulans membrane proteins. Gene. 2000;244:89-96 pubmed..Thus, these specific pauses might reflect a translational control over membrane protein targeting or early recognition ('+45 pause'), and over insertion or folding ('+70 pause'). ..
- Bürkle L, Cedzich A, Döpke C, Stransky H, Okumoto S, Gillissen B, et al. Transport of cytokinins mediated by purine transporters of the PUP family expressed in phloem, hydathodes, and pollen of Arabidopsis. Plant J. 2003;34:13-26 pubmed..In summary, three closely related PUPs are differentially expressed in Arabidopsis and at least two PUPs have properties similar to the adenine and cytokinin transport system identified in Arabidopsis cell cultures. ..
- Chirio M, Brethes D, Napias C, Grandier Vazeille X, Rakotomanana F, Chevallier J. Photoaffinity labelling of the purine-cytosine permease of Saccharomyces cerevisiae. Eur J Biochem. 1990;194:293-9 pubmed..Therefore this polypeptide corresponds to the purine-cytosine permease. ..
- Ferreira T, Brethes D, Pinson B, Napias C, Chevallier J. Functional analysis of mutated purine-cytosine permease from Saccharomyces cerevisiae. A possible role of the hydrophilic segment 371-377 in the active carrier conformation. J Biol Chem. 1997;272:9697-702 pubmed..This result suggests that the 371-377 segment might play a key role in the proper three-dimensional structure of the active purine-cytosine permease. ..
- Valdez Taubas J, Harispe L, Scazzocchio C, Gorfinkiel L, Rosa A. Ammonium-induced internalisation of UapC, the general purine permease from Aspergillus nidulans. Fungal Genet Biol. 2004;41:42-51 pubmed..These results provide further support for the occurrence of endocytosis and the lysosomal-endosomal function of the vacuolar compartment in A. nidulans. ..
- Weyand S, Shimamura T, Yajima S, Suzuki S, Mirza O, Krusong K, et al. Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter. Science. 2008;322:709-13 pubmed publisher..The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport. ..
- Yamamoto S, Inoue K, Murata T, Kamigaso S, Yasujima T, Maeda J, et al. Identification and functional characterization of the first nucleobase transporter in mammals: implication in the species difference in the intestinal absorption mechanism of nucleobases and their analogs between higher primates and other mammals. J Biol Chem. 2010;285:6522-31 pubmed publisher..The present study provides novel insights into the specific transport and metabolism of nucleobases and their analogs for therapeutic use. ..
- Diallinas G, Gorfinkiel L, Arst H, Cecchetto G, Scazzocchio C. Genetic and molecular characterization of a gene encoding a wide specificity purine permease of Aspergillus nidulans reveals a novel family of transporters conserved in prokaryotes and eukaryotes. J Biol Chem. 1995;270:8610-22 pubmed..Comparisons of the sequences and hydropathy profiles of members of this novel family of transporters yield insights into their structure, functionally important residues, and possible evolutionary relationships. ..
- Papageorgiou I, Yakob L, Al Salabi M, Diallinas G, Soteriadou K, De Koning H. Identification of the first pyrimidine nucleobase transporter in Leishmania: similarities with the Trypanosoma brucei U1 transporter and antileishmanial activity of uracil analogues. Parasitology. 2005;130:275-83 pubmed..Overall, the results show that, like purine nucleobase transport, pyrimidine nucleobase transport function is very similar in L. major and T. brucei insect forms. ..
- Natto M, Wallace L, Candlish D, Al Salabi M, Coutts S, de Koning H. Trypanosoma brucei: expression of multiple purine transporters prevents the development of allopurinol resistance. Exp Parasitol. 2005;109:80-6 pubmed..This study shows that transport-related resistance to purine antimetabolites is not easily induced in Trypanosoma spp. as long as uptake is mediated by multiple transporters. ..
- Mermelekas G, Georgopoulou E, Kallis A, Botou M, Vlantos V, Frillingos S. Cysteine-scanning analysis of helices TM8, TM9a, and TM9b and intervening loops in the YgfO xanthine permease: a carboxyl group is essential at ASP-276. J Biol Chem. 2010;285:35011-20 pubmed publisher..The data suggest that residues crucial for the transport mechanism cluster in two conserved motifs, at the cytoplasmic end of TM8 (EXXGDXXAT) and in TM9a (GXXXDG). ..
- Ortiz D, Sanchez M, Pierce S, Herrmann T, Kimblin N, Archie Bouwer H, et al. Molecular genetic analysis of purine nucleobase transport in Leishmania major. Mol Microbiol. 2007;64:1228-43 pubmed..The phenotypes of these null mutants underscore the importance of purine nucleobase transporters in the Leishmania life cycle and pharmacology. ..
- Maurino V, Grube E, Zielinski J, Schild A, Fischer K, Flügge U. Identification and expression analysis of twelve members of the nucleobase-ascorbate transporter (NAT) gene family in Arabidopsis thaliana. Plant Cell Physiol. 2006;47:1381-93 pubmed
- Bloch J, Sychrova H, Souciet J, Jund R, Chevallier M. Determination of a specific region of the purine-cytosine permease involved in the recognition of its substrates. Mol Microbiol. 1992;6:2989-97 pubmed..In particular, amino acids at position 374 and 377 modulate the affinity of the permease towards its substrates. In the wild-type, when asparagine is present at both of these positions, the lowest Kmapp values are found. ..
- Karena E, Frillingos S. Role of intramembrane polar residues in the YgfO xanthine permease: HIS-31 and ASN-93 are crucial for affinity and specificity, and ASP-304 and GLU-272 are irreplaceable. J Biol Chem. 2009;284:24257-68 pubmed publisher..Finally, one of the 17 assayable single-Cys mutants, Q258C, was sensitive to inactivation by N-ethylmaleimide. The findings suggest that polar residues important for the function of YgfO cluster in TMs 1, 3, 8 and 9a. ..
- Bone D, Hammond J. Nucleoside and nucleobase transporters of primary human cardiac microvascular endothelial cells: characterization of a novel nucleobase transporter. Am J Physiol Heart Circ Physiol. 2007;293:H3325-32 pubmed..Understanding the nucleoside and nucleobase transporter profiles in the vasculature will allow for further study into their roles in pathophysiological conditions such as hypoxia or ischemia. ..
- Witz S, Jung B, Fürst S, Möhlmann T. De novo pyrimidine nucleotide synthesis mainly occurs outside of plastids, but a previously undiscovered nucleobase importer provides substrates for the essential salvage pathway in Arabidopsis. Plant Cell. 2012;24:1549-59 pubmed publisher..Thus, a protein for the absolutely required import of pyrimidine nucleobases into plastids was identified...
- de Koning H, Al Salabi M, Cohen A, Coombs G, Wastling J. Identification and characterisation of high affinity nucleoside and nucleobase transporters in Toxoplasma gondii. Int J Parasitol. 2003;33:821-31 pubmed..gondii. ..
- Fedorova M, van de Mortel J, Matsumoto P, Cho J, Town C, VandenBosch K, et al. Genome-wide identification of nodule-specific transcripts in the model legume Medicago truncatula. Plant Physiol. 2002;130:519-37 pubmed..Nodule-enhanced expression was confirmed experimentally for the TCs composed of five or more ESTs, whereas the results for those TCs containing fewer ESTs were variable. ..
- Vickers M, Young J, Baldwin S, Ellison M, Cass C. Functional production of mammalian concentrative nucleoside transporters in Saccharomyces cerevisiae. Mol Membr Biol. 2001;18:73-9 pubmed..This work represents the development of a new model system for the functional production of recombinant nucleoside transporters of the CNT family of membrane proteins. ..
- Ferreira T, Chevallier J, Paumard P, Napias C, Brethes D. Screening of an intragenic second-site suppressor of purine-cytosine permease from Saccharomyces cerevisiae. Possible role of Ser272 in the base translocation process. Eur J Biochem. 1999;260:22-30 pubmed..The location and the observed decrease in the turnover of the carrier observed with the S272 L change lead us to propose that S272 could be part of a hydrophilic pore involved in the translocation of the base and/or the proton. ..
- Grandier Vazeille X, Neaud V, Geoffre S. Detection of purine cytosine permease of S. cerevisiae: use of antibodies against a synthetic peptide corresponding to a predicted sequence in the N-terminal domain of the protein. Biochem Biophys Res Commun. 1993;197:372-9 pubmed..These results demonstrate the specificity of the antisera and also suggest that the 45 kDa and 50 kDa proteins are both products of the FCY2 gene. ..
- Brethes D, Chirio M, Napias C, Chevallier M, Lavie J, Chevallier J. In vivo and in vitro studies of the purine-cytosine permease of Saccharomyces cerevisiae. Functional analysis of a mutant with an altered apparent transport constant of uptake. Eur J Biochem. 1992;204:699-704 pubmed..Therefore, we conclude that modification in the Ktapp of uptake in the strain carrying fcy2-21 allele is merely due to a modification of the binding ability of the permease for its ligands. ..
- Chen Y, Lo H, Wu C, Ko H, Chang T, Yang Y. Loss of heterozygosity of FCY2 leading to the development of flucytosine resistance in Candida tropicalis. Antimicrob Agents Chemother. 2011;55:2506-14 pubmed publisher..Subsequently, a combination of 5FC and another antifungal drug is applicable for treating infections of C. tropicalis...
- Amillis S, Kosti V, Pantazopoulou A, Mikros E, Diallinas G. Mutational analysis and modeling reveal functionally critical residues in transmembrane segments 1 and 3 of the UapA transporter. J Mol Biol. 2011;411:567-80 pubmed publisher..Our results are in agreement with a topological model of UapA built on the recently published structure of UraA, a bacterial homolog of UapA...
- Quashie N, Ranford Cartwright L, de Koning H. Uptake of purines in Plasmodium falciparum-infected human erythrocytes is mostly mediated by the human equilibrative nucleoside transporter and the human facilitative nucleobase transporter. Malar J. 2010;9:36 pubmed publisher..Inhibitors of hENT1 and hFNT1, as well as the NPP, should be considered in the development of anti-malarials targeted to purine transport. ..
- Mourad G, Tippmann Crosby J, Hunt K, Gicheru Y, Bade K, Mansfield T, et al. Genetic and molecular characterization reveals a unique nucleobase cation symporter 1 in Arabidopsis. FEBS Lett. 2012;586:1370-8 pubmed publisher..This is in stark contrast to the canonical transport profiles determined for the well-characterized S. cerevisiae NCS1 proteins FUR4 (uracil transport) or FCY2 (adenine, guanine, and cytosine transport). ..
- Schein J, Hunt K, Minton J, Schultes N, Mourad G. The nucleobase cation symporter 1 of Chlamydomonas reinhardtii and that of the evolutionarily distant Arabidopsis thaliana display parallel function and establish a plant-specific solute transport profile. Plant Physiol Biochem. 2013;70:52-60 pubmed publisher..The results suggest that the solute specificity for plant NCS1 occurred early in plant evolution and are distinct from solute transport specificities of single cell fungal NCS1 proteins. ..
- Karatza P, Panos P, Georgopoulou E, Frillingos S. Cysteine-scanning analysis of the nucleobase-ascorbate transporter signature motif in YgfO permease of Escherichia coli: Gln-324 and Asn-325 are essential, and Ile-329-Val-339 form an alpha-helix. J Biol Chem. 2006;281:39881-90 pubmed..4 mM, positions 323-329 are highly sensitive, with IC(50) values of 15-80 microM, and sensitivity of positions 330-340 follows a periodicity, with mutants sensitive to inactivation clustering on one face of an alpha-helix. ..
- Vlanti A, Diallinas G. The Aspergillus nidulans FcyB cytosine-purine scavenger is highly expressed during germination and in reproductive compartments and is downregulated by endocytosis. Mol Microbiol. 2008;68:959-77 pubmed publisher..FcyB-GFP was also shown to be downregulated by endocytosis in response to ammonia or the presence of cytosine. The expression profile of FcyB supports that its main physiological role is cytosine-purine scavenging. ..
- Rodriguez C, Bloch J, Chevallier M. The immunodetected yeast purine-cytosine permease is not N-linked glycosylated, nor are glycosylation sequences required to have a functional permease. Yeast. 1995;11:15-23 pubmed
- Papageorgiou I, De Koning H, Soteriadou K, Diallinas G. Kinetic and mutational analysis of the Trypanosoma brucei NBT1 nucleobase transporter expressed in Saccharomyces cerevisiae reveals structural similarities between ENT and MFS transporters. Int J Parasitol. 2008;38:641-53 pubmed..This point raises the possibility that ENT and MFS carriers, despite being considered evolutionarily distinct, might in fact share similar topologies and substrate translocations pathways. ..
- Wallace L, Candlish D, Hagos A, Seley K, De Koning H. Selective transport of a new class of purine antimetabolites by the protozoan parasite Trypanosoma brucei. Nucleosides Nucleotides Nucleic Acids. 2004;23:1441-4 pubmed..We show that these compounds display a remarkable selectivity for the parasite's transporters. The adenine analogue showed greater trypanocidal activity than the hypoxanthine or guanine analogues in vitro. ..
- Karatza P, Frillingos S. Cloning and functional characterization of two bacterial members of the NAT/NCS2 family in Escherichia coli. Mol Membr Biol. 2005;22:251-61 pubmed
- Bellofatto V. Pyrimidine transport activities in trypanosomes. Trends Parasitol. 2007;23:187-9; discussion 190 pubmed..The work by Gudin et al. characterizes the dynamics of these transporters and points to further areas for future genetic and therapeutic experiments. ..
- Kato R, Maeda T, Akaike T, Tamai I. Characterization of novel Na+-dependent nucleobase transport systems at the blood-testis barrier. Am J Physiol Endocrinol Metab. 2006;290:E968-75 pubmed..In conclusion, it was suggested that there might be purine- or pyrimidine-selective nucleobase transporters in rat Sertoli cells. ..
- Paluszynski J, Klassen R, Rohe M, Meinhardt F. Various cytosine/adenine permease homologues are involved in the toxicity of 5-fluorocytosine in Saccharomyces cerevisiae. Yeast. 2006;23:707-15 pubmed..Among these, Tpn1, Fur4 and the one encoded by yOR071c were found to contribute significantly to 5-FC toxicity, thus revealing alternative entry routes for 5-FC via other cytosine/adenine permease homologues. ..
- Brethes D, Napias C, Torchut E, Chevallier J. Purine-cytosine permease of Saccharomyces cerevisiae. Effect of external pH on nucleobase uptake and binding. Eur J Biochem. 1992;210:785-91 pubmed..9). The pK of this group remained similar to the value obtained with pAB4 when hypoxanthine was bound. From these data, it is proposed that the binding of hypoxanthine and H+ is a random process. ..
- Wagner R, Straub M, Souciet J, Potier S, De Montigny J. New plasmid system to select for Saccharomyces cerevisiae purine-cytosine permease affinity mutants. J Bacteriol. 2001;183:4386-8 pubmed..In this study, we developed a plasmid-based system that generated a number of affinity-mutated alleles, enabling us to define new amino acids critical for permease function. ..
- Chinnappan R, Dubé A, Lemay J, Lafontaine D. Fluorescence monitoring of riboswitch transcription regulation using a dual molecular beacon assay. Nucleic Acids Res. 2013;41:e106 pubmed publisher..This method is specific, reliable and could be applied at the high-throughput level for the identification of new potential antibiotics targeting any riboswitch-regulating gene expression at the mRNA level. ..
- Chapeland Leclerc F, Bouchoux J, Goumar A, Chastin C, Villard J, Noel T. Inactivation of the FCY2 gene encoding purine-cytosine permease promotes cross-resistance to flucytosine and fluconazole in Candida lusitaniae. Antimicrob Agents Chemother. 2005;49:3101-8 pubmed..The results of this study provide molecular evidence that inactivation of the sole FCY2 gene promotes cross-resistance to the antifungal association 5FC-FLC in C. lusitaniae. ..
- Hoque K, Chen L, Leung G, Tse C. A purine-selective nucleobase/nucleoside transporter in PK15NTD cells. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1988-95 pubmed publisher..This transporter is potentially important for transporting naturally occurring purines and purine analog drugs into cells. ..
- Wall M, Atterbury A, Dale N. Control of basal extracellular adenosine concentration in rat cerebellum. J Physiol. 2007;582:137-51 pubmed..The increased spatial and temporal resolution of the purine biosensor measurements has revealed the complexity of the control of adenosine and purine tone in the cerebellum. ..
- Amillis S, Hamari Z, Roumelioti K, Scazzocchio C, Diallinas G. Regulation of expression and kinetic modeling of substrate interactions of a uracil transporter in Aspergillus nidulans. Mol Membr Biol. 2007;24:206-14 pubmed..This model, which rationalizes the unique specificity of FurD for uracil, is compared to and found to be very similar to analogous models for protozoan uracil transporters. ..
- Pantazopoulou A, Diallinas G. Fungal nucleobase transporters. FEMS Microbiol Rev. 2007;31:657-75 pubmed..Apart from highlighting how a basic process such as nucleobase recognition and transport operates, this review intends to highlight features that might be applicable to antifungal pharmacology. ..
- Mansfield T, Schultes N, Mourad G. AtAzg1 and AtAzg2 comprise a novel family of purine transporters in Arabidopsis. FEBS Lett. 2009;583:481-6 pubmed publisher..Radio-labeled purine uptake experiments in yeast and in planta confirm the function of AtAzg1 and AtAzg2 as plant adenine-guanine transporters. ..
- Papakostas K, Georgopoulou E, Frillingos S. Cysteine-scanning analysis of putative helix XII in the YgfO xanthine permease: ILE-432 and ASN-430 are important. J Biol Chem. 2008;283:13666-78 pubmed publisher..The findings suggest that Ile-432 and Asn-430 of helix XII are crucial for purine uptake and affinity, and Asn-430 is probably at the vicinity of the binding site. ..
- Ortiz D, Sanchez M, Koch H, Larsson H, Landfear S. An acid-activated nucleobase transporter from Leishmania major. J Biol Chem. 2009;284:16164-9 pubmed publisher..These observations imply that LmaNT3 and LmaNT4 are nucleobase/proton symporters. ..
- Hope W, Tabernero L, Denning D, Anderson M. Molecular mechanisms of primary resistance to flucytosine in Candida albicans. Antimicrob Agents Chemother. 2004;48:4377-86 pubmed..A single resistant isolate, lacking the above polymorphism in FUR1, has a homozygous polymorphism in FCA1 that results in a glycine-to-aspartate substitution at position 28 in cytosine deaminase. ..
- Amillis S, Cecchetto G, Sophianopoulou V, Koukaki M, Scazzocchio C, Diallinas G. Transcription of purine transporter genes is activated during the isotropic growth phase of Aspergillus nidulans conidia. Mol Microbiol. 2004;52:205-16 pubmed..Similar results have been found in studies on the expression of other transporters in A. nidulans, suggesting that global expression of transporters might operate as a general system for sensing solute availability. ..
- Theisinger A, Grenacher B, Scharrer E. Na+ gradient-dependent transport of hypoxanthine by calf intestinal brush border membrane vesicles. J Comp Physiol B. 2003;173:165-70 pubmed..These findings represent the first demonstration of active Na(+) gradient-dependent nucleobase transport in intestinal brush border membrane vesicles. ..
- Sen Gupta S, Kerridge D, Chevallier M. A purine permease in Candida glabrata. FEMS Microbiol Lett. 1995;126:93-6 pubmed..glabrata. This differs from the purine cytosine permeases in Saccharomyces cerevisiae and Candida albicans which transport adenine, cytosine, guanine and hypoxanthine. ..
- Gournas C, Papageorgiou I, Diallinas G. The nucleobase-ascorbate transporter (NAT) family: genomics, evolution, structure-function relationships and physiological role. Mol Biosyst. 2008;4:404-16 pubmed publisher..Finally, we also discuss how modelling NAT-purine interactions might constitute a step towards the use of NAT proteins as specific gateways for targeting pathogenic microbes. ..