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2.A.71 The Folate-Biopterin Transporter (FBT) Family

The FBT family includes functionally characterized members from protozoa, cyanobacteria (Synechocystis) and plants (Arabidopsis thaliana). Functionally characterized members of the family include FT1 (TC# 2.A.71.1.3), the major protozoan folate transporter, BT1 (2.A.71.1.2), the biopterin/folate transporter and AdoMetT1, the major S-adenosylmethionine uptake porter (2.A.71.1.5). There are at least 6 homologues of the FT1 transporter in Leishmania encoded by tandem genes. A related protein in Trypanosoma brucei, ESAGIO, shows weak folate/biopterin transport activity.

Proteins of the FBT family are reported to contain 627-631 aas (Leishmania species), 408-431 aas (A. thaliana) and 453-494 aas (cyanobacteria). All probably have 12 TMSs. They may function by H+ symport. The FBT family is a distant family within the major facilitator superfamily (MFS; TC #2.A.1).

The probable transport reaction catalyzed by characterized FBT family members is:

[folate, biopterin or AdoMet] (out) + nH+ (out) → [folate, biopterin or AdoMet] (in) + nH+ (in).


This family belongs to the: MFS Superfamily.

References associated with 2.A.71 family:

Dridi, L., A. Ahmed Ouameur, and M. Ouellette. (2010). High affinity S-Adenosylmethionine plasma membrane transporter of Leishmania is a member of the folate biopterin transporter (FBT) family. J. Biol. Chem. 285: 19767-19775. 20406813
Eudes, A., E.R. Kunji, A. Noiriel, S.M. Klaus, T.J. Vickers, S.M. Beverley, J.F. Gregory, 3rd, and A.D. Hanson. (2010). Identification of transport-critical residues in a folate transporter from the folate-biopterin transporter (FBT) family. J. Biol. Chem. 285: 2867-2875. 19923217
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. 8183314
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. 3366764
Klaus, S.M., E.R. Kunji, G.G. Bozzo, A. Noiriel, R.D. de la Garza, G.J. Basset, S. Ravanel, F. Rebeille, J.F. Gregory, 3rd, and A.D. Hanson. (2005). Higher plant plastids and cyanobacteria have folate carriers related to those of trypanosomatids. J. Biol. Chem. 280: 38457-38463. 16162503
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. 10228149
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. 7984172
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. 11849635
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. 12023977