| 2.A.71 The Folate-Biopterin Transporter (FBT) Family
The FBT family includes functionally characterized members only from protozoa, but homologues are found in blue-green bacteria (Synechocystis) and plants (Arabidopsis thaliana). The functionally characterized members of the family include FT1, the major folate transporter, and BT1, the biopterin/folate transporter. There are at least 6 homologues of the FT1 transporter in Leishmania carried in a tandem array, but the genetic data suggest that only FT1 has appreciable activity (S. Beverley, personal communication). A related protein in Trypanosoma brucei, ESAGIO, shows weak folate/biopterin transport activity.
Proteins of the FBT family are reported to contain 686 aas (T. brucei), 627-631 aas (Leishmania species), 408-431 aas (A. thaliana) and 453 or 494 aas (cyanobacteria). All probably have 12 transmembrane α-helical spanners (TMSs). They may function by H+ symport. The FBT family is a distant family within the major facilitator superfamily (MFS; TC #2.A.1), most closely related to drug resistance permeases.
The probable transport reaction catalyzed by characterized FBT family members is:
[folate or biopterin] (out) + nH+ (out) → [folate or biopterin] (in) + nH+ (in).
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This family belongs to the MFS Superfamily.
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| References: |
Gottesdiener, K.M. (1994). A new VSG expression site-associated gene (ESAG) in the promoter region of Trypanosoma brucei encodes a protein with ten potential transmembrane domains. Mol. Biochem. Parasitol. 63: 143-151.
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Kaur, K., T. Coons, K. Emmett, and B. Ullman. (1988). Methotrexate-resistant Leishmania donovani genetically deficient in the folate-methotrexate transporter. J. Biol. Chem. 263: 7020-7028.
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Kundig, C., A. Haimeur, D. Legare, B. Papadopoulou, and M. Ouellette. (1999). Increased transport of pteridines compensates for mutations in the high affinity folate transporter and contributes to methotrexate resistance in the protozoan parasite Leishmania tarentolae. EMBO J. 18: 2342-2351.
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Myler, P.J., M.J. Lodes, G. Merlin, T. de Vos, and K.D. Stuart. (1994). An amplified DNA element in Leishmania encodes potential integral membrane and nucleotide-binding proteins. Mol. Biochem. Parasitol. 66: 11-20.
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Ouellette, M., J. Drummelsmith, A. El-Fadili, C. Kundig, D. Richard, and G. Roy. (2002). Pterin transport and metabolism in Leishmania and related trypanosomatid parasites. Int. J. Parasitol. 32: 385-398.
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Richard, D., C. Kundig, and M. Ouellette. (2002). A new type of high affinity folic acid transporter in the protozoan parasite Leishmania and deletion of its gene in methotrexate-resistant cells. J. Biol. Chem. 277: 29460-29467.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 2.A.71.1.1 | BT1 biopterin/folate (not methotrexate) transporter | Protozoa | BT1 (OrfG) of Leishmania donovani |
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| 2.A.71.1.2 | Biopterin transporter | Protozoa | BT1 of Leishmania mexicana |
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| 2.A.71.1.3 | FT1 folate/biopterin (not methotrexate) transporter | Protozoa | FT1 of Leishmania donovani |
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| 2.A.71.1.4 | FT1 (ESAG10) folate/biopterin transporter | Protozoa | ESAG10 of Trypanosoma brucei |
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| 2.A.71.2.1 | Functionally uncharacterized Orf | Cyano-bacteria | Orf of Synechococcus PCC7942 |
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| 2.A.71.3.1 | Functionally uncharacterized Orf | Plants | Orf of Arabidopsis thaliana |
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