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2.A.89 The Vacuolar Iron Transporter (VIT) Family

Members of the VIT family (DUF125) have been characterized in yeast (Ccc1; TC #2.A.89.1.1) and plants (Vit1; TC #2.A.89.1.2) (Kim et al., 2006). The former transports Fe2+ and Mn2+ into the vacuole where Fe2+ is stored, while the latter has been shown to transport Fe2+. Mutants accumulate excess Fe2+ in the cytoplasm which can be toxic. Excess Fe2+ is taken up into the vacuole. Vacuolar iron storage is critical for seedling development, and so is Vit1. Vit2 and Ccc1 have 5 putative TMSs in a 2 + 2 + 1 arrangement. Homologues are found in eukaryotes, bacteria and archaea where they may have a 1 + 2 + 2 arrangement (e.g., TC #2.A.89.2.1 from Pyrococcus abyssi) or a 1 + 2 + 3 arrangement (e.g., TC #2.A.89.3.1 from Burkholderia phytofirmans). Other bacterial and archaeal homologues are about 250 aas in length. A 270 aa homologue EAN12646 from Frankia sp. has 5 TMSs in a 2 + 3 arrangement. A 399 residue homologue from Ustilago maydis (EAK82927) has 5 putative TMSs in a 2 + 3 arrangement with two less hydrophobic peaks between the 2 and 3 strongly hydrophobic peaks. Of the two pairs of 2 TMSs, the first peak is smaller than the second peak in both cases, suggesting that these proteins arose by an intragenic duplication followed by addition of other domains. The separation between the 2 pairs is variable (>100 aas to <20 aas). These proteins may have an extended hydrophilic N-terminus. Eukaryotic VIT family proteins probably function by an H+ antiport carrier-type mechanism accounting for vacuolar uptake.

Ccc1/VIT1 homologs are widely distributed among organisms with the exception of animals. The recent elucidation of the crystal structure of a Ccc1/VIT1 plant ortholog has enabled the identification of both conserved and species-specific motifs required for metal transport. In Saccharomyces cerevisiae, multiple transcription factors including Yap5 and Msn2/Msn4 contribute to the expression of CCC1 under high-iron conditions. S. cerevisiae strains express a partially functional Ccc1 protein that renders them sensitive to iron. Different regulatory mechanisms have been described for non-Saccharomycetaceae Ccc1 homologs (Sorribes-Dauden et al. 2020).


References associated with 2.A.89 family:

Becker, P., R. Hakenbeck, and B. Henrich. (2009). An ABC transporter of Streptococcus pneumoniae involved in susceptibility to vancoresmycin and bacitracin. Antimicrob. Agents Chemother. 53: 2034-2041. 19273682
Bhubhanil S., Chamsing J., Sittipo P., Chaoprasid P., Sukchawalit R. and Mongkolsuk S. (2014). Roles of Agrobacterium tumefaciens membrane-bound ferritin (MbfA) in iron transport and resistance to iron under acidic conditions. Microbiology. 160(Pt 5):863-71. 24600024
Gollhofer, J., C. Schläwicke, N. Jungnick, W. Schmidt, and T.J. Buckhout. (2011). Members of a small family of nodulin-like genes are regulated under iron deficiency in roots of Arabidopsis thaliana. Plant Physiol. Biochem 49: 557-564. 21411332
Kato, T., K. Kumazaki, M. Wada, R. Taniguchi, T. Nakane, K. Yamashita, K. Hirata, R. Ishitani, K. Ito, T. Nishizawa, and O. Nureki. (2019). Crystal structure of plant vacuolar iron transporter VIT1. Nat Plants. [Epub: Ahead of Print] 30742036
Kim, S.A., Punshon, T., Lanzirotti, A., Li, L., Alonso, J.M., Ecker, J.R., Kaplan, J., and Guerinot, M.L. (2006). Localization of iron in Arabidopsis seed requires the vacuolar membrane transporter VIT1. Science 314: 1295-1298. 17082420
Li, L., O.S. Chen, D.M. Ward, and J. Kaplan. (2001). CCC1 is a transporter that mediates vacuolar iron storage in yeast. J. Biol. Chem. 276: 29515-29519. 11390404
Mohammad, A., Miranda-Rios, J., Navarrete, G.E., Quinto, C., Olivares, J.E., Garcia-Ponce, B., and Sanchez, F. (2004). Nodulin 22 from Phaseolus vulgaris protects Escherichia coli cells from oxidative stress. Planta 219: 993-1002. 15605176
Mydel, P., Takahashi, Y., Yumoto, H., Sztukowska, M., Kubica, M., Gibson, F.C., 3rd, Kurtz, D.M., Jr., Travis, J., Collins, L.V., Nguyen, K.A., Genco, C.A., and Potempa, J. (2006). Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection. PLoS Pathog. 2: e76. 16895445
Sorribes-Dauden, R., D. Peris, M.T. MartĂ­nez-Pastor, and S. Puig. (2020). Structure and function of the vacuolar Ccc1/VIT1 family of iron transporters and its regulation in fungi. Comput Struct Biotechnol J 18: 3712-3722. 33304466